Conformational changes in the Arp2 3 complex leading to actin nucleation Rodal, Avital Sokolova, Olga Robins, Deborah Daugherty, Karen Hippenmeyer, Simon ; https://orcid.org/0000-0003-2279-1061 Riezman, Howard Grigorieff, Nikolaus Goode, Bruce The two actin-related subunits of the Arp2/3 complex, Arp2 and Arp3, are proposed to form a pseudo actin dimer that nucleates actin polymerization. However, in the crystal structure of the inactive complex, they are too far apart to form such a nucleus. Here, we show using EM that yeast and bovine Arp2/3 complexes exist in a distribution among open, intermediate and closed conformations. The crystal structure docks well into the open conformation. The activator WASp binds at the cleft between Arp2 and Arp3, and all WASp-bound complexes are closed. The inhibitor coronin binds near the p35 subunit, and all coronin-bound complexes are open. Activating and loss-of-function mutations in the p35 subunit skew conformational distribution in opposite directions, closed and open, respectively. We conclude that WASp stabilizes p35-dependent closure of the complex, holding Arp2 and Arp3 closer together to nucleate an actin filament. Nature Publishing Group 2004 info:eu-repo/semantics/article doc-type:article text http://purl.org/coar/resource_type/c_2df8fbb1 https://research-explorer.ista.ac.at/record/3141 Rodal A, Sokolova O, Robins D, et al. Conformational changes in the Arp2 3 complex leading to actin nucleation. <i>Nature Structural and Molecular Biology</i>. 2004;12(1):26-31. doi:<a href="https://doi.org/10.1038/nsmb870">10.1038/nsmb870</a> eng info:eu-repo/semantics/altIdentifier/doi/10.1038/nsmb870 info:eu-repo/semantics/altIdentifier/issn/1545-9993 info:eu-repo/semantics/altIdentifier/e-issn/1545-9985 info:eu-repo/semantics/altIdentifier/pmid/15592479 info:eu-repo/semantics/closedAccess