The structure of the actin filament uncapping complex mediated by twinfilin

Dennis M. Mwangangi, Edward Manser, Robert C. Robinson

Research output: Contribution to journalArticlepeer-review

Abstract

Uncapping of actin filaments is essential for driving polymerization and depolymerization dynamics from capping protein-associated filaments; however, the mechanisms of uncapping leading to rapid disassembly are unknown. Here, we elucidated the x-ray crystal structure of the actin/twinfilin/capping protein complex to address the mechanisms of twinfilin uncapping of actin filaments. The twinfilin/capping protein complex binds to two G-actin subunits in an orientation that resembles the actin filament barbed end. This suggests an unanticipated mechanism by which twinfilin disrupts the stable capping of actin filaments by inducing a G-actin conformation in the two terminal actin subunits. Furthermore, twinfilin disorders critical actin-capping protein interactions, which will assist in the dissociation of capping protein, and may promote filament uncapping through a second mechanism involving V-1 competition for an actin-binding surface on capping protein. The extensive interactions with capping protein indicate that the evolutionary conserved role of twinfilin is to uncap actin filaments.

Original languageEnglish
Article numbereabd5271
JournalScience Advances
Volume7
Issue number5
DOIs
Publication statusPublished - Jan 27 2021

ASJC Scopus subject areas

  • General

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