title: Functional differences between the N-terminal domains of mouse and human myosin binding protein-C.
abstract: The N-terminus of cMyBP-C can activate actomyosin interactions in the absence of Ca2+, but it is unclear which domains are necessary. Prior studies suggested that the Pro-Ala rich region of human cMyBP-C activated force in permeabilized human cardiomyocytes, whereas the C1 and M-domains of mouse cMyBP-C activated force in permeabilized rat cardiac trabeculae. Because the amino acid sequence of the P/A region differs between human and mouse cMyBP-C isoforms (46% identity), we investigated whether species-specific differences in the P/A region could account for differences in activating effects. Using chimeric fusion proteins containing combinations of human and mouse C0, Pro-Ala, and C1 domains, we demonstrate here that the human P/A and C1 domains activate actomyosin interactions, whereas the same regions of mouse cMyBP-C are less effective. These results suggest that species-specific differences between homologous cMyBP-C isoforms confer differential effects that could fine-tune cMyBP-C function in hearts of different species.
authors.affiliation: Department of Neurobiology, Physiology and Behavior, University of California-Davis, Davis, CA 95616-8519, USA.
authors.forename: Justin F
authors.initials: JF
authors.lastname: Shaffer
authors.forename: Peony
authors.initials: P
authors.lastname: Wong
authors.forename: Kristina L
authors.initials: KL
authors.lastname: Bezold
authors.forename: Samantha P
authors.initials: SP
authors.lastname: Harris
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009068:Movement / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009218:Myosins / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D000099163:Myosin Binding Protein C
chemical_list: D002118:Calcium; D002352:Carrier Proteins; D009218:Myosins; D000099163:Myosin Binding Protein C