Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1016/j.abb.2014.03.007

Type

Journal article

Journal

Arch Biochem Biophys

Publication Date

01/05/2014

Volume

549

Pages

12 - 16

Keywords

ATPase cycle, Conformational change, Congenital myopathy, β-Tropomyosin, Actins, Actomyosin, Adenosine Triphosphatases, Animals, Humans, Muscle Fibers, Skeletal, Mutation, Protein Conformation, Rabbits, Tropomyosin