Cryo-EM of Human Arp2/3 Complexes Provides Structural Insights into Actin Nucleation Modulation by ARPC5 Isoforms

Overview

Journal Biol Open

Specialty Biology

Date 2020 Jul 15

PMID 32661131

Citations 15

Authors

Ottilie von Loeffelholz

Andrew Purkiss

Luyan Cao

Svend Kjaer

Naoko Kogata

Guillaume Romet-Lemonne

Michael Way

Carolyn A Moores

Affiliations

Soon will be listed here.

Abstract

The Arp2/3 complex regulates many cellular processes by stimulating formation of branched actin filament networks. Because three of its seven subunits exist as two different isoforms, mammals produce a family of Arp2/3 complexes with different properties that may be suited to different physiological contexts. To shed light on how isoform diversification affects Arp2/3 function, we determined a 4.2 Å resolution cryo-EM structure of the most active human Arp2/3 complex containing ARPC1B and ARPC5L, and compared it with the structure of the least active ARPC1A-ARPC5-containing complex. The architecture of each isoform-specific Arp2/3 complex is the same. Strikingly, however, the N-terminal half of ARPC5L is partially disordered compared to ARPC5, suggesting that this region of ARPC5/ARPC5L is an important determinant of complex activity. Confirming this idea, the nucleation activity of Arp2/3 complexes containing hybrid ARPC5/ARPC5L subunits is higher when the ARPC5L N-terminus is present, thereby providing insight into activity differences between the different Arp2/3 complexes.

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