The myosin-binding protein C motif binds to F-actin in a phosphorylation-sensitive manner

Justin F. Shaffer, Robert W. Kensler, Samantha P. Harris

Research output: Contribution to journalArticlepeer-review

177 Scopus citations


Cardiac myosin-binding protein C (cMyBP-C) is a regulatory protein expressed in cardiac sarcomeres that is known to interact with myosin, titin, and actin. cMyBP-C modulates actomyosin interactions in a phosphorylation-dependent way, but it is unclear whether interactions with myosin, titin, or actin are required for these effects. Here we show using cosedimentation binding assays, that the 4 N-terminal domains of murine cMyBP-C (i.e. C0-C1-m-C2) bind to F-actin with a dissociation constant (Kd) of ∼10 μM and a molar binding ratio (Bmax) near 1.0, indicating 1:1 (mol/mol) binding to actin. Electron microscopy and light scattering analyses show that these domains cross-link F-actin filaments, implying multiple sites of interaction with actin. Phosphorylation of the MyBP-C regulatory motif, or m-domain, reduced binding to actin (reduced Bmax) and eliminated actin cross-linking. These results suggest that theNterminus of cMyBP-C interacts with F-actin through multiple distinct binding sites and that binding at one or more sites is reduced by phosphorylation. Reversible interactions with actin could contribute to effects of cMyBP-C to increase crossbridge cycling.

Original languageEnglish (US)
Pages (from-to)12318-12327
Number of pages10
JournalJournal of Biological Chemistry
Issue number18
StatePublished - May 1 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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