The effect of the dilated cardiomyopathy-causing Glu40Lys TPM1 mutation on actin-myosin interactions during the ATPase cycle

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• 作者：Yurii S. Borovikov^a ; ^{boroviko@mail.cytspb.rssi.ru" rel="nofollow} ; Stanislava V. Avrova^a ; Olga E. Karpicheva^a ; Paul Robinson^b ; Charles S. Redwood^b
• 关键词：α ; -Tropomyosin ; Dilated cardiomyopathy ; Ghost muscle fibers ; ATPase cycle ; Polarized fluorescence
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2011
• 出版时间：5 August 2011
• 年：2011
• 卷：411
• 期：3
• 页码：496-500
• 全文大小：401 K

文摘

Dilated cardiomyopathy (DCM), characterized by cardiac dilatation and contractile dysfunction, is a major cause of heart failure. DCM can result from mutations in the gene encoding cardiac α-tropomyosin (TM). In order to understand how the dilated cardiomyopathy-causing Glu40Lys mutation in TM affects actomyosin interactions, thin filaments have been reconstituted in muscle ghost fibers by incorporation of labeled Cys707 of myosin subfragment-1 and Cys374 of actin with fluorescent probe 1.5-IAEDANS and α-tropomyosin (wild-type or Glu40Lys mutant). For the first time, the effect of these α-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. The Glu40Lys mutant TM inhibited these movements at the transition from AM^**·ADP·Pi to AM state, indicating a decrease of the proportion of the strong-binding sub-states in the actomyosin population. These structural changes are likely to underlie the contractile deficit observed in human dilated cardiomyopathy.