Structural evidence for the interaction of C-protein (MyBP-C) with actin and sequence identification of a possible actin-binding domain

JM Squire, PK Luther, C Knupp

Research output: Contribution to journalArticle (Academic Journal)peer-review

127 Citations (Scopus)

Abstract

C-protein (MyBP-C) is a myosin-binding protein that is usually seen in two sets of seven to nine positions in the C-zones in each half of the vertebrate striated muscle A-band. Skeletal muscle C-protein is a modular structure containing ten sub-domains (C1 to C10) of which seven are immunoglobulin-type domains and three (C6, C7 and C9) are fibronectin-like domains. Cardiac muscle C-protein has an extra N-terminal domain (C0) and also some sequence insertions, one of which provides phosphorylation sites. It is conceivable that C-protein has both a structural and regulatory role within the sarcomere. The precise mode of binding of C-protein to the myosin filament has not been determined. However, detailed ultrastructural studies have suggested that C-protein, which binds to myosin, can give rise to a longer periodicity (about 435 Å) than the intrinsic myosin filament repeat of 429 Å. The reason for this has remained a puzzle for over 25 years. Here we show by modelling and computation that the presence of this longer periodicity could be explained if the myosin-binding part of C-protein binds to myosin with the expected 429 Å repeat, but if there are systematic interactions of the N-terminal end of C-protein with the neighbouring actin filaments in the hexagonal lattice of filaments in the A-band. We also show that if they occur these interactions would probably only arise in defined muscle states. Further analysis of the MyBP-C sequence identifies a possible actin-binding domain in the Pro-Ala-rich sequence found at the N terminus of skeletal MyBP-C and between domains C0 and C1 in the cardiac sequence.
Translated title of the contributionStructural evidence for the interaction of C-protein (MyBP-C) with actin and sequence identification of a possible actin-binding domain
Original languageEnglish
Pages (from-to)713 - 724
Number of pages12
JournalJournal of Molecular Biology
Volume331 (3)
DOIs
Publication statusPublished - Aug 2003

Bibliographical note

Publisher: Academic Press

Fingerprint Dive into the research topics of 'Structural evidence for the interaction of C-protein (MyBP-C) with actin and sequence identification of a possible actin-binding domain'. Together they form a unique fingerprint.

Cite this