Mechanisms of Leiomodin 2-mediated Regulation of Actin Filament in Muscle Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2015 Sep 30

PMID 26417072

Citations 21

Authors

Xiaorui Chen

Fengyun Ni

Elena Kondrashkina

Jianpeng Ma

Qinghua Wang

Affiliations

Soon will be listed here.

Abstract

Leiomodin (Lmod) is a class of potent tandem-G-actin-binding nucleators in muscle cells. Lmod mutations, deletion, or instability are linked to lethal nemaline myopathy. However, the lack of high-resolution structures of Lmod nucleators in action severely hampered our understanding of their essential cellular functions. Here we report the crystal structure of the actin-Lmod2162-495 nucleus. The structure contains two actin subunits connected by one Lmod2162-495 molecule in a non-filament-like conformation. Complementary functional studies suggest that the binding of Lmod2 stimulates ATP hydrolysis and accelerates actin nucleation and polymerization. The high level of conservation among Lmod proteins in sequence and functions suggests that the mechanistic insights of human Lmod2 uncovered here may aid in a molecular understanding of other Lmod proteins. Furthermore, our structural and mechanistic studies unraveled a previously unrecognized level of regulation in mammalian signal transduction mediated by certain tandem-G-actin-binding nucleators.

Citing Articles

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