Species-specific differences in the Pro-Ala rich region of cardiac myosin binding protein-C

Justin F. Shaffer, Samantha P. Harris

Research output: Contribution to journalReview article

28 Scopus citations

Abstract

Cardiac myosin binding protein-C (cMyBP-C) is an accessory protein found in the A-bands of vertebrate sarcomeres and mutations in the cMyBP-C gene are a leading cause of familial hypertrophic cardiomyopathy. The regulatory functions of cMyBP-C have been attributed to the N-terminus of the protein, which is composed of tandem immunoglobulin (Ig)-like domains (C0, C1, and C2), a region rich in proline and alanine residues (the Pro-Ala rich region) that links C0 and C1, and a unique sequence referred to as the MyBP-C motif, or M-domain, that links C1 and C2. Recombinant proteins that contain various combinations of the N-terminal domains of cMyBP-C can activate actomy-osin interactions in the absence of Ca2+, but the specific sequences required for these effects differ between species; the Pro-Ala region has been implicated in human cMyBP-C whereas the C1 and M-domains appear important in mouse cMyBP-C. To investigate whether species-specific differences in sequence can account for the observed differences in function, we compared sequences of the Pro-Ala rich region in cMyBP-C isoforms from different species. Here we report that the numberofproline and alanine residuesinthe Pro-Ala rich region varies significantly between different species and that the number correlates directly with mammalian body size and inversely with heart rate. Thus, systematic sequence differences in the Pro-Ala rich region of cMyBP-C may contribute to observed functional differences in human versus mouse cMyBP-C isoforms and suggest that the Pro-Ala region may be important in matching contractile speed to cardiac function across species.

Original languageEnglish (US)
Pages (from-to)303-306
Number of pages4
JournalJournal of Muscle Research and Cell Motility
Volume30
Issue number7-8
DOIs
StatePublished - Dec 1 2009

Keywords

  • MyBP-C
  • Myosin binding protein-C
  • Proline-alanine
  • Sarcomere

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cell Biology

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