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(Circulation Research. 2006;98:1234.)
© 2006 American Heart Association, Inc.

Editorials

Myosin Binding Protein C in the Heart

Pieter P. de Tombe

From the Program in Cardiovascular Sciences, University of Illinois at Chicago.

Correspondence to Pieter P. de Tombe, PhD, Department of Physiology & Biophysics, 835 South Wolcott Ave MC 901, University of Illinois at Chicago, Chicago, IL 60612. E-mail pdetombe@uic.edu

See related article, pages 1290–1298

Key Words: myosin accessory proteins • sarcomere • cross-bridge cycling • regulation

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Myocardial force generation is initiated on the release of calcium ions from the sarcoplasmic reticulum and subsequent activation of the contractile apparatus.¹ A schematic of the cardiac sarcomere and some of its component proteins is shown in the Figure.² Contractile activation involves binding calcium to Tn-C, redistribution of the affinity of Tn-I for Tn-C away from Tn-T, and movement of tropomyosin on the thin filament, thereby exposing binding sites on actin. Binding of the myosin S1 domain to actin leads to cross-bridge force development. However, this simple two state model of muscle contraction is not sufficient to explain many features of muscle contraction.² For example, the rate of force development critically depends on the activation state of the thin filament.² Also, binding of a modified myosin (NEM-S1 which cannot hydrolyze ATP) has been shown to abolish this phenomenon.³ This, and other structural evidence, has led to the hypothesis that the thin filament must have at least three states: a blocked state (top left), where tropomyosin sterically blocks S1 binding; a closed state, induced by calcium binding to Tn-C, where tropomyosin has shifted away somewhat allowing weak interaction with the S1 domain; and an open state, where tropomyosin has moved away fully allowing for a strong interaction with S1 and force generation (bottom).² One interesting aspect of this theory is that the binding of myosin to actin by itself induces further activation of the thin filament, thus facilitating S1 domain binding along the filament; an elegant, yet simple molecular model of . . . [Full Text of this Article]

Related Article:

Activation of Myocardial Contraction by the N-Terminal Domains of Myosin Binding Protein-C

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Circ. Res. 2006 98: 1290-1298. [Abstract] [Full Text] [PDF]

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