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Journal of Biomedicine and Biotechnology
Volume 2010 (2010), Article ID 789798, 9 pages
doi:10.1155/2010/789798
Research Article

Functional Differences between the N-Terminal Domains of Mouse and Human Myosin Binding Protein-C

Justin F. Shaffer,1,2 Peony Wong,1 Kristina L. Bezold,1 and Samantha P. Harris1

1Department of Neurobiology, Physiology and Behavior, University of California-Davis, Davis, CA 95616-8519, USA
2Department of Bioengineering, University of Washington, Seattle, WA 98195-5061, USA

Received 16 December 2009; Accepted 31 January 2010

Academic Editor: Henk L. M. Granzier

Copyright © 2010 Justin F. Shaffer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The N-terminus of cMyBP-C can activate actomyosin interactions in the absence of C a 2 + , 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.