Conformational changes in the Arp2 3 complex leading to actin nucleation

A. Rodal, O. Sokolova, D. Robins, K. Daugherty, S. Hippenmeyer, H. Riezman, N. Grigorieff, B. Goode, Nature Structural and Molecular Biology 12 (2005) 26–31.

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Author
Rodal, Avital A; Sokolova, Olga; Robins, Deborah B; Daugherty, Karen M; Hippenmeyer, SimonIST Austria ; Riezman, Howard; Grigorieff, Nikolaus; Goode, Bruce L
Abstract
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.
Publishing Year
Date Published
2005-01-01
Journal Title
Nature Structural and Molecular Biology
Volume
12
Issue
1
Page
26 - 31
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Rodal A, Sokolova O, Robins D, et al. Conformational changes in the Arp2 3 complex leading to actin nucleation. Nature Structural and Molecular Biology. 2005;12(1):26-31. doi:10.1038/nsmb870
Rodal, A., Sokolova, O., Robins, D., Daugherty, K., Hippenmeyer, S., Riezman, H., … Goode, B. (2005). Conformational changes in the Arp2 3 complex leading to actin nucleation. Nature Structural and Molecular Biology, 12(1), 26–31. https://doi.org/10.1038/nsmb870
Rodal, Avital, Olga Sokolova, Deborah Robins, Karen Daugherty, Simon Hippenmeyer, Howard Riezman, Nikolaus Grigorieff, and Bruce Goode. “Conformational Changes in the Arp2 3 Complex Leading to Actin Nucleation.” Nature Structural and Molecular Biology 12, no. 1 (2005): 26–31. https://doi.org/10.1038/nsmb870.
A. Rodal et al., “Conformational changes in the Arp2 3 complex leading to actin nucleation,” Nature Structural and Molecular Biology, vol. 12, no. 1, pp. 26–31, 2005.
Rodal A, Sokolova O, Robins D, Daugherty K, Hippenmeyer S, Riezman H, Grigorieff N, Goode B. 2005. Conformational changes in the Arp2 3 complex leading to actin nucleation. Nature Structural and Molecular Biology. 12(1), 26–31.
Rodal, Avital, et al. “Conformational Changes in the Arp2 3 Complex Leading to Actin Nucleation.” Nature Structural and Molecular Biology, vol. 12, no. 1, Nature Publishing Group, 2005, pp. 26–31, doi:10.1038/nsmb870.

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