期刊
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
卷 1824, 期 2, 页码 366-373出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbapap.2011.11.004
关键词
alpha-Tropomyosin; Hypertrophy cardiomyopathy; Ghost muscle fiber; ATPase cycle; Polarized fluorescence
资金
- Russian Fund for Fundamental Research [11-04-00244a]
- British Heart Foundation
- BHF Centre of Research Excellence, Oxford
- European Community [241577]
Hypertrophic cardiomyopathy (HCM), characterized by cardiac hypertrophy and contractile dysfunction, is a major cause of heart failure. HCM can result from mutations in the gene encoding cardiac alpha-tropomyosin (TM). To understand how the HCM-causing Asp175Asn and Glu180Gly mutations in alpha-tropomyosin affect on actin-myosin interaction during the ATPase cycle, we labeled the SH1 helix of myosin subfragment-1 and the actin subdomain-1 with the fluorescent probe N-iodoacetyl-N'-(5-sulfo-1-naphtylo)ethylenediamine. These proteins were incorporated into ghost muscle fibers and their conformational states were monitored during the ATPase cycle by measuring polarized fluorescence. For the first time, the effect of these alpha-tropomyosins on the mobility and rotation of subdomain-1 of actin and the SH1 helix of myosin subfragment-1 during the ATP hydrolysis cycle have been demonstrated directly by polarized fluorimetry. Wild-type alpha-tropomyosin increases the amplitude of the SH1 helix and subdomain-1 movements during the ATPase cycle, indicating the enhancement of the efficiency of the work of cross-bridges. Both mutant TMs increase the proportion of the strong-binding substates, with the effect of the Glu180Gly mutation being greater than that of Asp175Asn. It is suggested that the alteration in the concerted conformational changes of actomyosin is likely to provide the structural basis for the altered cardiac muscle contraction. (C) 2011 Elsevier B.V. All rights reserved.
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