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(Circulation Research. 2002;91:656.)
© 2002 American Heart Association, Inc.

Editorials

Structure-Function Relationships in Myosin Binding Protein-C

Taking Off the Blinders and Collaring Hypertrophic Cardiomyopathy

Jeffrey Robbins, D. Woodrow Benson

From the Department of Pediatrics, Divisions of Pediatric Cardiology (D.W.B.) and Molecular Cardiovascular Biology (D.W.B., J.R.), The Children’s Hospital Research Foundation, Cincinnati, Ohio.

Correspondence to J. Robbins, PhD, Division of Molecular Cardiovascular Biology, MLC 7020, 3333 Burnet Avenue, Cincinnati, OH 45229-3039. E-mail jeff.robbins@chmcc.org

Key Words: hypertrophic cardiomyopathy • myosin binding protein-C • thick filaments • transgenic animal models

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

Myosin binding protein-C (MyBP-C), a major component of the thick filament, binds to both the myosin (thick) and titin filament systems through defined domains and is believed to make an important contribution to sarcomere structure. Discovered over 27 years ago,¹ interest in the protein’s role(s) intensified after familial hypertrophic cardiomyopathy (FHC) was linked to chromosome 11p13-q13, where cardiac MyBP-C (MYBPC3) is encoded.² Reports of MYBPC3 mutations in FHC appeared a short time later.³ Over 30 heterozygous MYBPC3 mutations have been identified in subsequent studies; less than half have been missense mutations, whereas the remainder are nonsense mutations predicted to result in truncated polypeptides. Age-dependent penetrance is a characteristic feature of the MyBP-C phenotype. For example, hypertrophy is not evident in nearly 50% of mutant carriers before the age of 40 years, whereas by 60 years, hypertrophy occurs in more than 90%.⁴ These patients generally have favorable survival when compared to individuals with mutations in other genes causing FHC, but the MyBP-C mutations can result in sudden cardiac-related death.

MyBP-C is localized in the inner two-thirds of the A band, the so-called C zone (Figure).⁵ Negative staining and optical diffraction techniques reveal 11 transverse bands that are approximately 60 nm wide. Antibody staining shows that MyBP-C is restricted to the outer 7 to 9 axial bands, which are spaced approximately 43 nm apart in each half-sarcomere.^1,6,7 This particular organization implies some functional sequelae: MyBP-C can only interact with certain myosin molecules and these, in turn, will interact . . . [Full Text of this Article]

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