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TitleCryo-EM of human Arp2/3 complexes provides structural insights into actin nucleation modulation by ARPC5 isoforms.
Journal, issue, pagesBiol Open, Vol. 9, Issue 7, Year 2020
Publish dateJul 31, 2020
AuthorsOttilie von Loeffelholz / Andrew Purkiss / Luyan Cao / Svend Kjaer / Naoko Kogata / Guillaume Romet-Lemonne / Michael Way / Carolyn A Moores /
PubMed AbstractThe 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 ...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.
External linksBiol Open / PubMed:32661131 / PubMed Central
MethodsEM (single particle)
Resolution4.2 - 4.5 Å
Structure data

EMDB-10959, PDB-6yw6:
Cryo-EM structure of the ARP2/3 1B5CL isoform complex.
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-10960, PDB-6yw7:
Cryo-EM structure of the ARP2/3 1A5C isoform complex.
Method: EM (single particle) / Resolution: 4.5 Å

Chemicals

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

Source
  • homo sapiens (human)
KeywordsSTRUCTURAL PROTEIN / Cytoskeleton

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