The E117K mutation in β-tropomyosin disturbs concerted conformational changes of actomyosin in muscle fibers.

Journal article

The effect of the skeletal myopathy-causing E117K mutation in human β-tropomyosin on actomyosin structure during the ATPase cycle was studied using fluorescent probes bound to actin subdomain 1 and the myosin head. Multistep changes in flexural rigidity of actin filament and in spatial arrangement of actin subdomain 1 and myosin SH1 helix in troponin-free ghost muscle fibers were revealed. During the ATPase cycle E117K tropomyosin inhibited the rotation of subdomain 1 by 46% and the tilt of the SH1 helix by 49% compared with wild-type. At strong-binding stages the proportion of strong binding sub-states in the actomyosin population is decreased by the mutation. At weak-binding stages abnormally high numbers of switched-on actin monomers were observed, thus indicating a disturbance in concerted conformational changes of actomyosin. These structural alterations are likely to underlie the contractile deficit observed with this mutation.

Authors: Karpicheva, O; Redwood, C; Borovikov, Y

• Publication status: Published
• Publisher: Academic Press Inc.
• Journal: Archives of biochemistry and biophysics
• Volume: 549
• Pages: 12-16
• Publication date: 2014-05-01
• DOI: 10.1016/j.abb.2014.03.007
• EISSN: 1096-0384
• ISSN: 0003-9861
• Language: English
• Keywords: Humans; Actomyosin; Mutation; Muscle Fibers, Skeletal; Rabbits; Protein Conformation; Tropomyosin; Animals; Actins; Adenosine Triphosphatases