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Molecular Consequences of the Myopathy-Related D286G Mutation on Actin Function.

Authors :
Fan J
Chan C
McNamara EL
Nowak KJ
Iwamoto H
Ochala J
Source :
Frontiers in physiology [Front Physiol] 2018 Dec 04; Vol. 9, pp. 1756. Date of Electronic Publication: 2018 Dec 04 (Print Publication: 2018).
Publication Year :
2018

Abstract

Myopathies are notably associated with mutations in genes encoding proteins known to be essential for the force production of skeletal muscle fibers, such as skeletal alpha-actin. The exact molecular mechanisms by which these specific defects induce myopathic phenotypes remain unclear. Hence, in the present study, to better understand actin dysfunction, we conducted a molecular dynamic simulation together with ex vivo experiments of the specific muscle disease-causing actin mutation, D286G located in the actin-actin interface. Our computational study showed that D286G impairs the flexural rigidity of actin filaments. However, upon activation, D286G did not have any direct consequences on actin filament extension. Hence, D286G may alter the structure of actin filaments but, when expressed together with normal actin molecules, it may only have minor effects on the ex vivo mechanics of actin filaments upon skeletal muscle fiber contraction.

Details

Language :
English
ISSN :
1664-042X
Volume :
9
Database :
MEDLINE
Journal :
Frontiers in physiology
Publication Type :
Academic Journal
Accession number :
30564146
Full Text :
https://doi.org/10.3389/fphys.2018.01756