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Cryo-EM of human Arp2/3 complexes provides structural insights into actin nucleation modulation by ARPC5 isoforms.
Biol Open. 2020 Jul 31; 9(7)BO

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.

Authors+Show Affiliations

Department of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK.The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.Université de Paris, CNRS, Institut Jacques Monod, 75013 Paris, France.The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.Université de Paris, CNRS, Institut Jacques Monod, 75013 Paris, France.The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK michael.way@crick.ac.uk c.moores@mail.cryst.bbk.ac.uk. Department of Infectious Disease, Imperial College London, London W2 1PG, UK.Department of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK michael.way@crick.ac.uk c.moores@mail.cryst.bbk.ac.uk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32661131

Citation

von Loeffelholz, Ottilie, et al. "Cryo-EM of Human Arp2/3 Complexes Provides Structural Insights Into Actin Nucleation Modulation By ARPC5 Isoforms." Biology Open, vol. 9, no. 7, 2020.
von Loeffelholz O, Purkiss A, Cao L, et al. Cryo-EM of human Arp2/3 complexes provides structural insights into actin nucleation modulation by ARPC5 isoforms. Biol Open. 2020;9(7).
von Loeffelholz, O., Purkiss, A., Cao, L., Kjaer, S., Kogata, N., Romet-Lemonne, G., Way, M., & Moores, C. A. (2020). Cryo-EM of human Arp2/3 complexes provides structural insights into actin nucleation modulation by ARPC5 isoforms. Biology Open, 9(7). https://doi.org/10.1242/bio.054304
von Loeffelholz O, et al. Cryo-EM of Human Arp2/3 Complexes Provides Structural Insights Into Actin Nucleation Modulation By ARPC5 Isoforms. Biol Open. 2020 Jul 31;9(7) PubMed PMID: 32661131.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cryo-EM of human Arp2/3 complexes provides structural insights into actin nucleation modulation by ARPC5 isoforms. AU - von Loeffelholz,Ottilie, AU - Purkiss,Andrew, AU - Cao,Luyan, AU - Kjaer,Svend, AU - Kogata,Naoko, AU - Romet-Lemonne,Guillaume, AU - Way,Michael, AU - Moores,Carolyn A, Y1 - 2020/07/31/ PY - 2020/7/15/pubmed PY - 2020/7/15/medline PY - 2020/7/15/entrez KW - Actin KW - Arp2/3 KW - Cryo-EM KW - Cytoskeleton KW - Isoforms KW - Nucleation JF - Biology open JO - Biol Open VL - 9 IS - 7 N2 - 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. SN - 2046-6390 UR - https://www.unboundmedicine.com/medline/citation/32661131/Cryo-EM_of_human_Arp2/3_complexes_provides_structural_insights_into_actin_nucleation_modulation_by_ARPC5_isoforms L2 - http://bio.biologists.org/cgi/pmidlookup?view=long&pmid=32661131 DB - PRIME DP - Unbound Medicine ER -
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