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L. Carrier, G. Bonne, E. Bahrend, B. Yu, P. Richard, F. Niel, B. Hainque, C. Cruaud, F. Gary, S. Labeit, J. B. Bouhour, O. Dubourg, M. Desnos, A. A. Hagege, R. J. Trent, M. Komajda, M. Fiszman and K. Schwartz, “Organization and Sequence of Human Cardiac Myosin Binding Protein C Gene (MYBPC3) and Identification of Mutations Predicted to Produce Truncated Proteins in Familial Hypertrophic Cardiomyopathy,” Circulation Research, Vol. 80, No. 3, 1997, pp. 427-434.

has been cited by the following article:

• TITLE: Feline Hypertrophic Cardiomyopathy Associated with the p.A31P Mutation in cMyBP-C Is Caused by Production of Mutated cMyBP-C with Reduced Binding to Actin

  AUTHORS: Mia T. N. Godiksen, Craig Kinnear, Tina Ravnsborg, Peter Højrup, Sara Granström, Inga A. Laursen, Paula L. Hedley, Johanna C. Moolman-Smook, William J. McKenna, Jørgen Koch, Michael Christiansen

  KEYWORDS: Feline; HCM; cMyBP-C; Mutation; Actin; Y2H; MSMS

  JOURNAL NAME: Open Journal of Veterinary Medicine, Vol.3 No.2, June 6, 2013

  ABSTRACT: Hypertrophic cardiomyopathy (HCM) is a myocardial disorder, with complications including heart failure, thromboemboli and sudden death. Human and feline HCM (fHCM) are clinically comparable, thus fHCM may serve as a spontaneous animal model. fHCM in Maine Coon (MC) cats is associated with the p.A31P mutation in the cMyBP-C protein. The mutation is located in the cMyBP-C C0-domain which is known to interact with actin. The presence and levels of the wild type and mutated protein in heart tissue from mutant and wild type MC cats were examined by SDS-PAGE and mass spectrometry (MS). Quantitative yeast-2-hybrid (Y2H) protein-protein interaction analysis was used to assess the effect of the mutation on C0C1/actin interaction. The NMR-based structure of the C0 domain was used to calculate the energetic consequence of replacing alanine with a proline residue. In the homozygous MC cat, the mutated cMyBP-C protein was present, and cMyBPC-C levels were not reduced compared to that of the wild type cat. However, the interaction of actin with mutant cMyBP-C C0C1 was reduced compared to that of wild type. This may be because the substitution of the alanine with proline in position 31 was energetically highly unfavorable and resulted in only one hydrogen bond within the anti-parallel beta-strand compared to two hydrogen-bonds for alanine, possibly destabilizing the structure of the actin-interacting domain. The p.A31P mutation is present in cardiac tissue and the most likely pathogenic mechanism is interference with contractility by reducing binding of the C0C1 domain of cMyBP-C to actin.