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Journal of Biomedicine and Biotechnology
Volume 2011 (2011), Article ID 435271, 12 pages
Research Article

Facilitated Cross-Bridge Interactions with Thin Filaments by Familial Hypertrophic Cardiomyopathy Mutations in α-Tropomyosin

1Department of Biological Science, The Florida State University, Tallahassee, FL 32306-4295, USA
2Department of Neurobiology, College of Basic Medical Science, Southern Medical University, Guangzhou 510515, China
3Donders Institute for Brain, Cognition and Behavior, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, 6500 HB Nijmegen, The Netherlands
4Department of Biology, American University in Cairo, Cairo 11835, Egypt
5Department of Biomedical Sciences, The Florida State University College of Medicine, Tallahassee, FL 32306, USA
6Institute of Molecular Biophysics, The Florida State University, Tallahassee, FL 32306, USA
7Department of Mathematics, The Florida State University, Tallahassee, FL 32306, USA
8Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA
9QIAGEN Inc., Valencia, CA 91355, USA
10Department of Physics, The Florida State University, Tallahassee, FL 32306, USA
11Hitachi Global Storage Technologies, San Jose Research Center, San Jose, CA 95135, USA
12Agilent Technologies Inc., Santa Clara, CA 95051, USA

Received 1 June 2011; Accepted 24 August 2011

Academic Editor: Guy Benian

Copyright © 2011 Fang Wang 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.


Familial hypertrophic cardiomyopathy (FHC) is a disease of cardiac sarcomeres. To identify molecular mechanisms underlying FHC pathology, functional and structural differences in three FHC-related mutations in recombinant α-Tm (V95A, D175N, and E180G) were characterized using both conventional and modified in vitro motility assays and circular dichroism spectroscopy. Mutant Tm's exhibited reduced α-helical structure and increased unordered structure. When thin filaments were fully occupied by regulatory proteins, little or no motion was detected at pCa 9, and maximum speed (pCa 5) was similar for all tropomyosins. Ca2+-responsiveness of filament sliding speed was increased either by increased pCa50 (V95A), reduced cooperativity n (D175N), or both (E180G). When temperature was increased, thin filaments with E180G exhibited dysregulation at temperatures ~10°C lower, and much closer to body temperature, than WT. When HMM density was reduced, thin filaments with D175N required fewer motors to initiate sliding or achieve maximum sliding speed.