3dxm Citations

Characterization of two classes of small molecule inhibitors of Arp2/3 complex.

Abstract

Polymerization of actin filaments directed by the actin-related protein (Arp)2/3 complex supports many types of cellular movements. However, questions remain regarding the relative contributions of Arp2/3 complex versus other mechanisms of actin filament nucleation to processes such as path finding by neuronal growth cones; this is because of the lack of simple methods to inhibit Arp2/3 complex reversibly in living cells. Here we describe two classes of small molecules that bind to different sites on the Arp2/3 complex and inhibit its ability to nucleate actin filaments. CK-0944636 binds between Arp2 and Arp3, where it appears to block movement of Arp2 and Arp3 into their active conformation. CK-0993548 inserts into the hydrophobic core of Arp3 and alters its conformation. Both classes of compounds inhibit formation of actin filament comet tails by Listeria and podosomes by monocytes. Two inhibitors with different mechanisms of action provide a powerful approach for studying the Arp2/3 complex in living cells.

Articles - 3dxm mentioned but not cited (6)

  1. Characterization of two classes of small molecule inhibitors of Arp2/3 complex. Nolen BJ, Tomasevic N, Russell A, Pierce DW, Jia Z, McCormick CD, Hartman J, Sakowicz R, Pollard TD. Nature 460 1031-1034 (2009)
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  3. Cryo-EM reveals the transition of Arp2/3 complex from inactive to nucleation-competent state. Shaaban M, Chowdhury S, Nolen BJ. Nat Struct Mol Biol 27 1009-1016 (2020)
  4. Synthetic triterpenoids target the Arp2/3 complex and inhibit branched actin polymerization. To C, Shilton BH, Di Guglielmo GM. J Biol Chem 285 27944-27957 (2010)
  5. Cryo-EM of human Arp2/3 complexes provides structural insights into actin nucleation modulation by ARPC5 isoforms. von Loeffelholz O, Purkiss A, Cao L, Kjaer S, Kogata N, Romet-Lemonne G, Way M, Moores CA. Biol Open 9 bio054304 (2020)
  6. A Burst of Genetic Innovation in Drosophila Actin-Related Proteins for Testis-Specific Function. Schroeder CM, Valenzuela JR, Mejia Natividad I, Hocky GM, Malik HS. Mol Biol Evol 37 757-772 (2020)


Reviews citing this publication (23)

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Articles citing this publication (287)