Published online before print February 7, 2002, doi: 10.1161/01.RES.0000012666.42782.30
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© 2002 American Heart Association, Inc.
Molecular Medicine |
Intramolecular Interaction of SUR2 Subtypes for Intracellular ADP-Induced Differential Control of KATP Channels
From the Departments of Pharmacology II (K.M., T.M., A.F., Y.K.) and Ophthalmology (K.M., T.F., Y.T.), Graduate School of Medicine, and the Research Center For Structural Biology (H.N.), Institute for Protein Research, Osaka University, Suita, Osaka, Japan; and the Division of Science of Biological Supramolecular Systems (K.K.), Graduate School of Integrated Science, Yokohama University, Yokohama, Kanagawa, Japan.
Correspondence to Y. Kurachi, Dept of Pharmacology II, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. E-mail ykurachi{at}pharma2.med.osaka-u.ac.jp
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Abstract |
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ATP-sensitive K+ (KATP) channels are composed of sulfonylurea receptors (SURs) and inwardly rectifying Kir6.2-channels. The C-terminal 42 amino acid residues (C42) of SURs are responsible for ADP-induced differential activation of KATP channels in SUR-subtypes. By examining ADP-effect on KATP channels containing various chimeras of SUR2A and SUR2B, we identified a segment of 7 residues at central portion of C42 critical for this phenomenon. A 3-D structure model of the region containing the second nucleotide-binding domain (NBD2) of SUR and C42 was developed based on the structure of HisP, a nucleotide-binding protein forming the bacterial Histidine transporter complex. In the model, the polar and charged residues in the critical segment located within a distance that allows their electrostatic interaction with Arg1344 at the Walker-A loop of NBD2. Therefore, the interaction might be involved in the control of ADP-induced differential activation of SUR2-subtype KATP channels.
Key Words: homology modeling • KATP channel • nucleotide binding domain • sulfonylurea receptor • Walker motif
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Introduction |
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ATP-sensitive K+ (KATP) channels are inhibited by intracellular ATP and activated by nucleoside diphosphates and thus provide a link between the metabolic state and cellular excitability in various organs, including pancreas, heart, vasculature, and brain.1 These channels are associated with such cellular functions as insulin secretion, cardiac preconditioning, vasodilatation, and neurotransmitter release. KATP channels are heterooctamers composed of an ATP-binding cassette protein, known as the sulfonylurea receptor (SUR), and an inwardly rectifying K+ channel (Kir) subunit, Kir6.0.2,3 Three kinds of SUR, SUR1, SUR2A, and SUR2B, have been isolated and their roles in formation of functional K+ channels with Kir6.0 subunits have been extensively examined.2–6 It is now widely accepted that SUR1, SUR2A, and SUR2B represent pancreatic, cardiac, and vascular smooth muscle types of SUR, respectively. When expressed with Kir6.2, all 3 subtypes of SUR form KATP channels that exhibit the same single-channel characteristics; weak inward-rectification and a unitary conductance of
80 pS in the inward-direction with 150 mmol/L extracellular K+. They, however, show distinct sensitivities to different vasorelaxant K+ channel opener compounds (KCOs), intracellular MgADP, and sulfonylurea drug derivatives.7–11 The different pharmacological sensitivities depend on the SUR-subtype. SUR has been assigned to the ATP-binding-cassette (ABC) superfamily, as is assumed to possess 17 transmembrane segments and 2 nucleotide-binding domains (NBDs) with Walker-A and -B consensus motifs for binding intracellular nucleotides.12,13 However, structural elements of SURs and their functional roles responsible for their different features have not been fully determined.
The majority of ABC proteins are active transporters, utilizing the energy of ATP hydrolysis to pump solutes and small substances across the membrane. SUR on the other hand regulates the behavior of Kir6.0 channel pores, and thus, the role of the 2 NBDs differs from those of other ABC-proteins.12 In SUR, it is thought that NBD1 binds MgATP and that NBD2 binds MgADP and/or binds and hydrolyzes MgATP. The binding of MgADP to NBD2 causes activation of KATP channels.9,14–15 Depending on the subtype of SUR, the sensitivity of KATP channels to MgADP is divergent. KATP channels containing SUR1 or SUR2B can be effectively activated by ADP, whereas those containing SUR2A require much higher concentrations of ADP. SUR2A and SUR2B are generated from a single gene and differ only in their splicing site, which is the 42 amino acid residue C-terminal tail (C42).5 The C42 region of SUR2B shares 30% amino acid sequence homology with that of SUR2A but 70% with that of SUR1. Therefore, C42 should play a critical role in the SUR subtype-dependent activation of KATP channels by MgADP.16 Recently, we showed that C42 of SUR2A, but not that of either SUR2B or SUR1, was able to reduce stimulation of KATP channels by ADP acting via NBD2.17
The purpose of this study is to obtain further insight into the role of C42 on KATP channel-activation by ADP via NBD2, by using electrophysiological and 3-D structural model analyses with different chimeras of SUR2A and SUR2B. We found that the middle segment of C42 composed of 7 amino acids are critical for differential effects of ADP on SUR2-subtype KATP channels. In the 3-D models, the polar and charged residues in the segment located within a distance that allows their electrostatic interaction with Arg1344 on the Walker-A loop of NBD2.
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Materials and Methods |
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Molecular Biology
The cDNAs of mouse Kir6.2 and SURs were used.5,11 The coding region of each cDNA was individually subcloned into an expression vector, pcDNA3 (Invitrogen, San Diego, Calif). All chimeric cDNAs and cassette mutants were formed between C42s of SUR2A and SUR2B. Chimeric cDNA and mutant constructs were produced using the Splicing by Overlap Extension (SOE) PCR technique as previously described29 and Quick Change Site-Directed Mutagenesis Kit (STRATAGENE). All chimeric and mutated SURs were confirmed by DNA sequencing.
Functional Coexpression of SURs and Kir6.2 cDNAs
The plasmid containing Kir6.2 was cotransfected with wild-type or chimeric SURs into human embryonic kidney (HEK) 293T cells using LipofectAMINE (Life Technology, Inc). To monitor the efficiency of transfection, pCA-GFP (S65A) was also cotransfected. The cells expressing green fluorescent protein (GFP) were identified by fluorescence microscopy and used for electrophysiology.
Electrophysiology
The channels expressed in the cotransfected HEK293T cells were recorded in the inside-out configuration of the patch clamp technique. The tip of pipettes were coated with Sylgard and heat-polished. The bath was perfused with a solution containing (in mmol/L) 150 KCl, 5 EGTA, 2 MgCl2, and 5 HEPES-KOH (pH 7.3), in which the concentration of free Mg2+ was adjusted to 1.4 mmol/L. Pipettes were filled with a solution containing (in mmol/L) 150 KCl, 1 MgCl2, 1 CaCl2, and 5 HEPES-KOH (pH 7.4). Single channel ion currents were recorded in excised membrane patches voltage-clamped at -60 mV membrane potential. All experiments were performed at room temperature (25°C). The data were recorded on videocassette tapes with a PCM converter system (VR-10B, Instrutech Corp). They were reproduced, low-pass filtered at 1 kHz (-3 dB) by an 8-pole Bessel filter (Frequency Devices), sampled at 5 kHz, and analyzed off-line on a computer (Macintosh G3, Apple Computer Inc) using commercially available software. The channel activity was expressed as relative NPo (rNPo) with reference to the maximum NPo measured in the absence of intracellular nucleotides in each inside-out patch. All data were derived from at least 6 distinct patches and expressed as mean±standard error (SE).
Homology Modeling and Validation of Second Nucleotide Binding Domains in SUR2s
The whole cytosolic region containing second nucleotide-binding domain (NBD2) and C42 of SUR2A and SUR2B were determined by knowledge-based homology modeling using the program Modeler4.19 The input consisted of a sequence alignment of the SUR-NBD2/C42s and HisP or MalK and MJ1267, and coordinates obtained from the Rutgers Protein Data Bank for crystal structure of HisP, MalK, and MJ1267 (PDB ID: 1B0U, 1G29, and 1G6H, respectively). ADP was modeled by coordinating it to the equivalent residues that were determined for HisP. Models in figures were prepared using InsightII2000 (Molecular Simulations Inc). Quality of models were determined by stereochemical properties (using PROCHECK20) and root mean standard deviation calculated in InsightII2000.
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The Responses to Intracellular ADP of ATP-Sensitive K+ Channels Containing Different SUR2 Subtypes and Homology Models of Their C-Terminal Cytosolic Regions
The responses of ATP-sensitive K+ (KATP) channels composed of Kir6.2 and either SUR2A or SUR2B are shown in Figure 1A. HEK293T cells were cotransfected with Kir6.2 and one of the wild-type SUR2s. On formation of inside-out patches vigorous KATP channel activity appeared in both cases. ATP (1 mmol/L) added to the internal solution almost completely suppressed channel activity. The activity of SUR2A/Kir6.2 channels was only weakly enhanced by ADP; ADP exhibited practically no effect at 30 µmol/L and enhanced channel activity only weakly at 300 µmol/L. Even with 1 mmol/L ADP, the relative NPo of SUR2A/Kir6.2 channels was
0.13 of the maximum activity. On the other hand, ADP effectively enhanced SUR2B/Kir6.2 channel-activity in a concentration-dependent fashion (see also the top panels of Figure 2C). To evaluate the responses to ADP of KATP channels containing the differential type of SUR, we defined 2 parameters, Imax and EC50. Imax is the maximum value of KATP channel activity induced by ADP with reference to that in the absence of nucleotides; EC50 is the concentration of ADP at the half-maximum channel activity. The Imax value of the wild-type SUR2A/Kir6.2 channel was 0.15, which was around one third of that (0.43) of wild-type SUR2B/Kir6.2. The EC50 value for SUR2A/Kir6.2 was 250 µmol/L ADP, which was 9 times larger than that for SUR2B/Kir6.2 (Table).
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-helices are colored light green and ß-strands colored blue.) Some conserved motifs (Walker-A, Walker-B, Q-loop, D-loop, signature, and switch) are boxed in orange. The C42 region is enclosed in the red box. C, Models were built based on the X-ray crystal structure of HisP
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Most ABC proteins bind intracellular nucleotides by using recognition of phosphates at the Walker-A segment of a nucleotide-binding domain. The C42-region is located 150 amino acids away from Walker-A, and thus, a specific interaction between the 2 segments was not obvious (Figure 1B). Therefore, we developed 3-D structure models of the cytosolic C-termini of SUR2A and B that contain both NBD2 and C42 with the homology modeling technique. We adopted the structure of HisP as the template because of the following reasons. (1) HisP is an intracellular component of Histidine permease, an ABC superfamily protein whose 3-D crystal structure is available at the atomic level.18 (2) Histidine permease binds nucleotides at its Walker-motifs that correspond to those in SURs. (3) Alignment between HisP and SUR2-NBD2/C42 shows high conservation of some motifs and overall identity of 21% in the region. Furthermore, the secondary structures of the region containing NBD2 and C42 in SUR2s are predicted to show high similarity to that of HisP (Figure 1B). Therefore, it seemed reasonable to construct homology models of the entire C-terminal cytosolic regions of SUR2s based on the HisP structure. These models were developed using MODELLER4 (Figure 1C).19 The geometrical qualities of the models were examined by a program PROCHECK, which provided the acceptable high scores for the developed models (see online Figure 1B that can be found in the online data supplement available at http://www.circresaha. org and the following results of PROCHECK).20 The SUR-NBD2/C42 models were also constructed using the structures of other nucleotide-binding proteins, MalK and MJ1267, as the templates for evaluation of the models constructed on HisP.21,22 The details of this examination are also provided in the online data supplement. These evaluations indicated that the SUR2-NBD2/C42 models developed from HisP, MalK, and MJ1267 structures were very similar from each other. Thus, the structure of the region containing NBD2 and C42 might be conserved among various ABC transporters, and the developed models based on HisP may be usable for present analyses. In the models of both SUR2A and SUR2B, C42 was located close to the Walker-A segment of NBD2.
Structure-Based Chimeric Study of the Effect of the C42 Region on KATP Channel Activity
To identify the critical part of C42, we constructed chimeric SURs of SUR2A and SUR2B by dividing their C42 into 3 portions (Figure 2A). Because the homology models predicted that 2 putative ß strands (ß11 and ß12 with a turn) in C42 were located very close to the Walker-A in NBD2, the middle portion used to construct chimera was designed to contain both ß11 and ß12. The designation AAA indicates the 3 sections of C42 to consist of wild-type SUR2A, whereas BBB represents those of wild-type SUR2B. The left portion (A.. or B..) was composed of amino acids 1505 to 1510, the middle portion (.A. or .B.) was amino acids 1511 to 1529, and the right portion (..A or ..B) amino acids 1530 to 1546. Chimeras constructed on this plan are shown in Figure 2A.
Figure 2B shows examples of the responses of KATP channels composed of 2 chimeric SURs (ABA and BAB) and Kir6.2 to ADP. Figure 2C summarizes the results obtained from the different chimeric SUR2s. When the middle portion of C42 was adopted from SUR2A (.A.), the KATP channel activity induced by ADP was almost similar to that of wild-type SUR2A/Kir6.2 channels (AAA) in Imax and EC50. On the other hand, when the portion was from SUR2B (.B.), the channel’s response was similar to that of KATP channels containing wild-type SUR2B (Table). The middle portion of C42 thus appeared to be mainly responsible for the different activation of KATP channels by ADP.
The middle portion of C42 (amino acids 1511 to 1529) was further dissected. It was divided into 3 parts with each part being designated as "a" if derived from SUR2A and designated as "b" if derived from SUR2B (Figure 3A). The first part (a.. or b..) consisted of amino acids 1511 to 1515, the second part (.a. or .b.) consisted of amino acids 1516 to 1525, and the third part (..a or ..b) consisted of amino acids 1526 to 1529. KATP channels containing chimeric SURs where the second part of middle portion of C42 consisted of 2A type (.a.) were only slightly activated by high concentrations of ADP (AbabA and BbabB in Figure 3B and the top panels in Figure 2C) and thus corresponded to the behavior of the entire wild-type SUR2A (Table). On the other hand, when the second part of middle portion of C42 consisted of 2B type (.b.), the KATP channels were effectively activated by as little as 30 µmol/L ADP (BabaB and AabaA in Figure 3B and the bottom panels in Figure 3C; Table) and thus corresponded to the behavior of the entire wild-type SUR2B. It is worthy of note that chimera AabaA, which consisted of SUR2A except for amino acids 1516 to 1525, showed a response to ADP typical of SUR2B, although the equivalent chimera of SUR2B, BbabB, showed a reaction to ADP typical of SUR2A. It is thus clear that the 10 amino acid residues 1516 to 1525, which include the turn between ß11and ß12, are essential for differential activation of KATP channels by ADP.
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Critical Residues in the 1516 to 1525 Amino Acid Region of SUR
When the 10 amino acid residues in positions 1516 to 1525 are compared between SUR2A and SUR2B, there are 2 characteristic polar and charged residues at positions 1517 and 1518 in ß 11. In SUR2A, they are polar Ser (S) and negatively charged Glu (E), and positively charged Lys (K) and Arg (R) in SUR2B. From the 3-D model, these residues are expected to be closely located to a positively charged residue Arg (R) on the Walker-A motif in NBD2 (Figure 4C) because the distance in the model between each Cß ranged from 7.3- to 8.9-Å. Therefore, we constructed mutant SURs where these charged residues were either exchanged between SUR2A and SUR2B or altered to Ala (Figure 4A). Exchanging positively charged KR for polar and negatively charged SE in SUR2B resulted in behavior similar to SUR2A (Figure 4B and Table). But, exchanging SE for KR in SUR2A had no effect, and the behavior of the KATP channels remained typical of SUR2A. Canceling the charge at position 1518 in SUR2B abolished the high efficacy and sensitivity to ADP of the channels while canceling that at position 1517 showed less effect (Table). These results suggest that the positively charged residues, especially Arg 1518, in ß11 of SUR2B are necessary but not sufficient to impose the high efficacy and sensitivity of KATP channels to MgADP.
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The next section therefore attempted to determine what other amino acids in this region of SUR2B needed to be added to the positively charged Lys and Arg to impose high efficacy and sensitivity to ADP to SUR2A. The 10 amino acid residues in positions 1516 to 1525 were divided into 3 segments. Segment 1 consisted of amino acids 1516 to 1518, segment 2 consisted of amino acids 1519 to 1522, and segment 3 consisted of amino acids 1523 to 1525. A schematic representation of the constructed mutants is shown in Figure 5A where segments are designated as a' or b' representing residues derived from SUR2A or SUR2B, respectively. The addition of Met at position 1516 to Lys and Arg at positions 1517 and 1518 (chimera Aab'a'a'aA) was not sufficient to evoke high efficacy and sensitivity to ADP in SUR2A. Further addition of segment 3 from SUR2B (chimera Aab'a'b'aA) was also without effect. However, a chimera that contained segments 1 and 2 from SUR2B (chimera Aab'b'a'aA) was able to reconstitute the response of SUR2B to ADP in the SUR2A backbone (Figure 5B and Table). This effect was abolished when the first residue of these 2 segments, Met1516, was replaced by the equivalent Phe from SUR2A (chimera Aab'b'a'aA [M1516F]). Thus, the 7 residues 1516 to 1522 in C42 appeared to be necessary and enough to confer 2B-type response to SUR2A.
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Charged Residues in the Walker-A Motif of NBD2 Also Play a Critical Role in ADP-Mediated Channel Activation
The next question we addressed was how the positively charged residues, Lys and Arg, in C42 of SUR2B control the function of the Walker-A loop in NBD2. There exist 2 positively-charged residues in the Walker-A, Arg1344 and Lys1348 (Figure 6A). Lys1348 is thought to be the binding site of ADP to the Walker-A,9,14,15,23–26 whereas Arg1344 is located near the N-terminal edge of the Walker-A and is not thought to be directly involved in ADP binding. The homology model indicated that this Arg residue located within the distance to interact with the positively charged residues, Lys and Arg, in SUR2B-C42 (Figure 5C and Figure 6A). The mutation of Arg1344 to Ala caused as large reduction of ADP-induced channel activity as that of mutating Lys1348 to Met (Figures 6B and 6C). Therefore, Arg1344 may be somehow functionally involved in control of Walker-A function such as ADP binding.
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This study has revealed that a segment of 7 amino acids in the middle portion of C42 is critical for the SUR2 subtype-dependent, ADP-induced differential activation of KATP channels. The homology structure models developed based on HisP structure suggest that the polar and charged residues in the segment locate within a distance that allows electrostatic interaction with Arg1344 at Walker-A of NBD2. In this study, channel activity was used as a functional readout to arrive at a mechanistic explanation for SUR function. Thus, we could not identify the function of NBD2 responsible for the ADP-induced alteration in channel activity. The candidates may include ADP binding at Walker-A, ATPase-activity at NBD2, and control of interaction between SUR and Kir6.2.26 Because it was reported that NBD2 of SUR2B exhibits higher binding capability to ADP than that of SUR2A27 and because the primary function of Walker-A loop is to bind nucleotides, it seems likely that the difference between SUR2A and SUR2B in the binding property of ADP to their NBD2 may be one of the most possible candidates. However, further studies are needed to identify the function of NBD2 responsible for the ADP-induced alteration of KATP channel activity.
The polar and charged residues in the middle portion of C42 may be critical to control the sensitivity of NBD2 to ADP. Because in the homology model, the polar and charged residues located within a distance that allows electrostatic interaction with Arg1344 at Walker A, one possibility is that the conformation of the Walker-A loop might be affected by the interaction. In SUR2A, the residues are polar Ser and negatively charged Glu, whereas they are positively charged Lys and Arg in SUR2B. Therefore, the possible electrostatic interaction between Arg1344 and C42 is expected to be in the opposite sense between SUR2A and SUR2B, which might be important for the SUR2 subtype-dependent differential effects of ADP on KATP channels. It was found, however, that the polar and charged resides in C42 were not sufficient to explain the difference (Figure 4). A segment of 7 amino acid residues of SUR2B containing the polar and charged residues were found necessary to increase the sensitivity of SUR2A to ADP (Figure 5C). The homology models showed that this segment would form a ß-turn. The head of the segment (Phe in SUR2A, Met in SUR2B) was located very close to the back of the Walker-A segment in the model (Figures 4C and 5C). Thus, the ß-turn and Walker-A would interact sterically over a short distance. A number of amino acids surrounding the polar and charged residues in the segment are hydrophobic and thus might also have a steric effect for arranging the positions of the polar and charged residues to locate within appropriate distance from Walker-A.
The candidate amino acid at Walker-A loop for possible electrostatic interaction with the polar and charged residues in C42 was identified Arg1344 in the model. Although Arg1344 localized at the edge of Walker-A is thought not to be directly involved in the binding of ADP to the loop, SUR2B(R1344A) abolished ADP-induced KATP channel activation as the mutant at the putative ADP-binding site in Walker-A, SUR2B(K1348M). This result may be in line with the notion that the polar and charged residues in C42 were within the distance that allows electrostatic interaction with Arg1344. Therefore, one possibility is that the electrostatic interaction between the polar and charged residues in C42 and Arg1344 is involved in the control of SUR2 subtype-dependent, ADP-induced differential activation of KATP channels. Resolution of the actual protein structure of SUR, however, is needed to further examine this possibility.
The roles of some of the structural elements in both SUR and Kir6.0 in the behavior of functional KATP channels have been clarified. The transmembrane domains of SUR1 are needed for the interaction with Kir6.2, whereas the first transmembrane segment (M1) and the N-terminus of Kir6.2 are involved in the interaction with SUR.28 N-terminus of Kir6.2 is also critically involved in the control of channel gating,29 because both cytosolic N- and C-termini of Kir6.2 interact to form the ATP-binding pocket for closure of KATP channels.30–34 In native KATP channel proteins C-terminus of SUR1 and N-terminus of Kir6.2 are closely located.34 Therefore, alteration in the conformation of C-terminus of a SUR induced by ADP action on NBD2 at Walker-A may affect channel gating via its interaction with Kir6.2 N-terminus. Recently, a dramatic alteration in the conformation of NBD especially at the linker region between Walker-A and -B motifs (signature sequence) by nucleotide binding to Walker-A was predicted in the crystallization analysis of ADP-bound MJ1267.22 Thus, alteration in the conformation of NBD2 induced by ADP binding to Walker-A might be an indispensable step in the ADP-induced activation of KATP channels. Further studies are needed to clarify in SUR2-subtypes the relation between the ADP-induced alteration in the conformation of NBD2 and the critical segment in the center portion of C42.
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Acknowledgments |
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This work was supported by the Grant-in-Aid for Specific Research on Priority Area (B) (12144207) (to Y.K.) from the Ministry of Education, Science, Sports and Culture of Japan, by a grant from the Research for the Future Program of the Japanese Society for the Promotion of Science (96L00302) (to Y.K.), by "Research Grant for Cardiovascular Disease" (11C-1) from the Ministry of Health and Welfare of Japan (to Y.K.), and by a grant from Vehicle Racing Commemorative Foundation (to Y.K.). We thank Dr Ian Findlay for his critical comments on this article.
Received October 23, 2001; revision received January 29, 2002; accepted January 30, 2002.
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References |
|---|
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
1. Ashcroft FM. Adenosine 5'-triphosphate-sensitive potassium channels. Annu Rev Neurosci. 1988; 11: 97–118.[CrossRef][Medline] [Order article via Infotrieve]
2.
Aguilar-Bryan L, Nichols CG, Wechsler SW, Clement JPIV, Boyd AEIII, Gonzalez G, Herrera-Sosa H, Nguy K, Bryan J, Nelson DA. Cloning of the ß cell high-affinity sulfonylurea receptor: a regulator of insulin secretion. Science. 1995; 268: 423–426.
3.
Inagaki N, Gonoi T, Clement JPIV, Namba N, Inazawa J, Gonzalez G, Aguilar-Bryan L, Seino S, Bryan J. Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science. 1995; 270: 1166–1170.
4. Inagaki N, Gonoi T, Clement JPIV, Wang C-Z, Aguilar-Bryan L, Bryan J, Seino S. A family of sulfonylurea receptors determines the pharmacological properties of ATP sensitive K+ channels. Neuron. 1996; 16: 1011–1017.[CrossRef][Medline] [Order article via Infotrieve]
5.
Isomoto S, Kondo C, Yamada M, Matsumoto S, Higashiguchi O, Horio Y, Matsuzawa Y, Kurachi Y. A novel sulfonylurea receptor forms with BIR (Kir6.2) a smooth muscle type ATP-sensitive K+ channel. J Biol Chem. 1996; 271: 24321–24324.
6.
Yamada M, Isomoto S, Matsumoto S, Kondo C, Shindo T, Horio Y, Kurachi Y. Sulphonylurea receptor 2B and Kir6.1 form a sulphonylurea-sensitive but ATP-insensitive K+ channel. J Physiol. 1997; 499: 715–720.
7. Nichols CG, Shyng SL, Nestorowicz A, Glaser B, Clement JPVI, Gonzalez G, Aguilar-Bryan L, Permutt MA, Bryan J. Adenosine diphosphate as an intracellular regulator of insulin secretion. Science. 1996; 272: 1785–1787.[Abstract]
8.
Gribble FM, Tucker SJ, Ashcroft FM. The interaction of nucleotides with the tolbutamide block of cloned ATP-sensitive K+ channel currents expressed in Xenopus oocytes: a reinterpretation. J Physiol. 1997; 504: 35–45.
9. Gribble FM, Tucker SJ, Ashcroft FM. The essential role of the Walker-A motifs of SUR1 in K-ATP channel activation by Mg-ADP and diazoxide. EMBO J. 1997; 16: 1145–1152.[CrossRef][Medline] [Order article via Infotrieve]
10.
Shyng S, Ferrigni T, Nichols CG. Regulation of KATP channel activity by diazoxide and MgADP. Distinct functions of the two-nucleotide binding folds of the sulfonylurea receptor. J Gen Physiol. 1997; 110: 643–654.
11. Shindo T, Yamada M, Isomoto S, Horio Y, Kurachi Y. SUR2 subtype (A and B)-dependent differential activation of the cloned ATP-sensitive K+ channels by pinacidil and nicorandil. Br J Pharmacol. 1998; 124: 985–991.[CrossRef][Medline] [Order article via Infotrieve]
12. Higgins CF. The ABC of channel regulation. Cell. 1995; 82: 693–696.[CrossRef][Medline] [Order article via Infotrieve]
13. Tusnady GE, Bakos E, Varadi A, Sarkadi B. Membrane topology distinguishes a subfamily of the ATP-binding cassette (ABC) transporters. FEBS Lett. 1997; 402: 1–3.[CrossRef][Medline] [Order article via Infotrieve]
14.
Ueda K, Inagaki N, Seino S. MgADP antagonism to Mg2+-independent ATP binding of the sulfonylurea receptor SUR1. J Biol Chem. 1997; 272: 22983–22986.
15. Ueda K, Matsuo M, Tanabe K, Morita K, Kioka N, Amachi T. Comparative aspects of the function and mechanism of SUR1 and MDR1 protein. Biochim Biophys Acta. 1999; 1461: 305–313.[Medline] [Order article via Infotrieve]
16. Reimann F, Gribble FM, Ashcroft FM. Differential response of KATP channels containing SUR2A or SUR2B subunits to nucleotides and pinacidil. Mol Pharmacol. 2000; 58: 1318–1325.[Medline] [Order article via Infotrieve]
17.
Matsuoka T, Matsushita K, Katayama Y, Fujita A, Inageda K, Tanemoto M, Inanobe A, Yamashita Y, Matsuzawa Y, Kurachi Y. C-terminal tails of sulfonylurea receptors control ADP-induced activation and diazoxide modulation of ATP-sensitive K+ channel Circ Res. 2000; 87: 873–880.
18. Hung L-W, Wang IX, Nikaido K, Liu P-Q, Ames G F, Kim S-H. Crystal structure of the ATP-binding subunit of an ABC transporter. Nature. 1998; 396: 703–707.[CrossRef][Medline] [Order article via Infotrieve]
19. Sali A, Blundell TL. Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol. 1993; 234: 779–815.[CrossRef][Medline] [Order article via Infotrieve]
20. Laskowski RA, MacArthur MW, Moss DS, Thornton JM. PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crys. 1993; 26: 283–291.[CrossRef]
21. Diederichs K, Diez J, Greller G, Muller C, Breed J, Schnell C, Vonrhein C, Boos W, Welte W. Crystal structure of MalK, the ATPase subunit of the trehalose/maltose ABC transporter of archaeon Thermococcus litoralis. EMBO J. 2000; 19: 5951–5961.[CrossRef][Medline] [Order article via Infotrieve]
22. Karpowich N, Martsinkevich O, Millen L, Yuan Y, Dai PL, MacVey K, Thomas PJ, Hunt JF. Crystal structures of the MJ1267 ATP binding cassette reveal an induced-fit effect at the ATPase active site of an ABC transporter. Structure. 2001; 9: 571–586.[Medline] [Order article via Infotrieve]
23.
Tagaya M, Yagami T, Fukui T. Affinity labeling of adenylate kinase with adenosine diphosphopyridoxal: presence of Lys21 in ATP-binding site. J Biol Chem. 1987; 262: 8257–8261.
24.
Azzaria M, Schurr E, Gros P. Discrete mutations introduced in the predicted nucleotide binding sites of the mdr1 gene abolish its ability to confer multidrug resistance. Mol Cell Biol. 1989; 9: 5289–5297.
25.
D’hahan N, Moreau C, Prost A-L, Jacquet H, Alekseev AE, Terzic A, Vivaudou M. Pharmacological plasticity of cardiac ATP-sensitive potassium channels toward diazoxide revealed by ADP. Proc Natl Acad Sci U S A. 1999; 96: 12162–12167.
26. Zingman LV, Alekseev AE, Bienengraber M, Hodgson D, Karger AB, Dzeja PP, Terzic A. Signaling in channel/enzyme multimers: ATPase transitions in SUR module gate ATP-sensitive K+ conductance. Neuron. 2001; 31: 233–245.[CrossRef][Medline] [Order article via Infotrieve]
27.
Matsuo M, Tanabe K, Kioka N, Amachi T, Ueda K. Different binding properties and affinities for ATP and ADP among sulfonylurea receptor subtypes, SUR1, SUR2A, and SUR2B. J Biol Chem. 2000; 275: 28757–28763.
28. Schwappach B, Zerangue N, Jan YN, Jan LY. Molecular basis for KATP assembly: transmembrane interactions mediate association of a K+ channel with an ABC transporter. Neuron. 2000; 26: 155–167.[CrossRef][Medline] [Order article via Infotrieve]
29. Kondo C, Repunte VP, Satoh E, Yamada M, Horio Y, Matsuzawa Y, Pott L, Kurachi Y. Chimeras of Kir6.1 and Kir6.2 reveal structural elements involved in spontaneous opening and unitary conductance of the ATP-sensitive K+ channels. Receptors Channels. 1998; 6: 129–140.[Medline] [Order article via Infotrieve]
30. Tucker SJ, Gribble FM, Proks P, Trapp S, Ryder TJ, Haug T, Reimann F, Ashcroft FM. Molecular determinants of KATP channel inhibition by ATP. EMBO J. 1998; 17: 3290–3296.[CrossRef][Medline] [Order article via Infotrieve]
31.
Tucker SJ, Ashcroft FM. Mapping of the physical interaction between the intracellular domains of an inwardly rectifying potassium channel, Kir6.2. J Biol Chem. 1999; 274: 33393–33397.
32.
Koster JC, Sha Q, Shyng S, Nichols CG. ATP inhibition of KATP channels: control of nucleotide sensitivity by the N-terminal domain of the Kir6.2 subunit. J Physiol. 1999; 515: 19–30.
33.
Proks P, Gribble FM, Adhikari R, Tucker SJ, Ashcroft F. Involvement of the N-terminus of Kir6.2 in the inhibition of the KATP channel by ATP. J Physiol. 1999; 514: 19–25.
34. Clement JPIV, Kunjilwar K, Gonzalez G, Schwanstecher M, Panten U, Aguilar-Bryan L, Bryan J. Association and stoichiometry of KATP channel subunits. Neuron. 1997; 18: 827–838.[CrossRef][Medline] [Order article via Infotrieve]
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