Cryo-EM of human Arp2/3 complexes provides structural insights into actin nucleation modulation by ARPC5 isoforms

Autor: Svend Kjaer, Luyan Cao, Guillaume Romet-Lemonne, Ottilie von Loeffelholz, Andrew Purkiss, Michael Way, Carolyn A. Moores, Naoko Kogata
Přispěvatelé: Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Models
Molecular
Gene isoform
Protein Conformation
Cryo-electron microscopy
QH301-705.5
[SDV]Life Sciences [q-bio]
nucleation
Science
Nucleation
macromolecular substances
Biology
bcs
General Biochemistry
Genetics and Molecular Biology
Actin-Related Protein 2-3 Complex
Protein filament
Structure-Activity Relationship
03 medical and health sciences
0302 clinical medicine
Humans
Biology (General)
Cytoskeleton
Actin
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
Actin nucleation
0303 health sciences
Chemistry
030302 biochemistry & molecular biology
Cryoelectron Microscopy
isoforms
cytoskeleton
Actins
Actin Cytoskeleton
Mutation
Biophysics
arp2/3
cryo-em
biological phenomena
cell phenomena
and immunity
General Agricultural and Biological Sciences
actin
030217 neurology & neurosurgery
Function (biology)
Research Article
Protein Binding
Zdroj: Biology Open, Vol 9, Iss 7 (2020)
Biology Open
Biology Open, Royal Society, 2020, 9 (7), pp.bio054304. ⟨10.1242/bio.054304⟩
article-version (VoR) Version of Record
ISSN: 2046-6390
DOI: 10.1242/bio.054304⟩
Popis: 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.
Summary: The Arp2/3 complex stimulates formation of branched actin filament networks and exhibits isoform diversity in mammals. We show how different Arp2/3 subunit isoforms contribute to differences in complex function.
Databáze: OpenAIRE
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