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Conformational changes in the Arp2/3 complex leading to actin nucleation
Avital A Rodal1, Olga Sokolova, Deborah B Robins
1Department of Biology, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454, USA.
Nature Structural & Molecular Biology
|December 14, 2004
Summary
The Arp2/3 complex, crucial for actin polymerization, exists in multiple conformations. Activator WASp induces a closed state, bringing Arp2 and Arp3 subunits together for filament nucleation.
Area of Science:
- Cell Biology
- Biochemistry
- Structural Biology
Background:
- The Arp2/3 complex is essential for initiating actin filament formation.
- Its two actin-related subunits, Arp2 and Arp3, are hypothesized to form a nucleus for polymerization.
- Previous crystal structures showed these subunits too distant for nucleation.
Purpose of the Study:
- To investigate the conformational states of the Arp2/3 complex.
- To determine how activators and inhibitors influence these conformations.
- To elucidate the mechanism of Arp2/3 complex-mediated actin nucleation.
Main Methods:
- Electron microscopy (EM) was used to analyze yeast and bovine Arp2/3 complexes.
- Conformational states (open, intermediate, closed) were identified.
- The binding sites and effects of activator WASp and inhibitor coronin were studied.
Main Results:
- Arp2/3 complexes exist in a dynamic equilibrium of open, intermediate, and closed conformations.
- The crystal structure aligns with the open conformation.
- WASp binding at the Arp2-Arp3 cleft drives the complex to a closed state.
- Coronin binding near the p35 subunit favors an open state.
- Mutations in p35 alter conformational distribution, favoring closed or open states.
Conclusions:
- The Arp2/3 complex undergoes conformational changes.
- WASp binding stabilizes a p35-dependent closed conformation.
- This closure brings Arp2 and Arp3 subunits into proximity for actin nucleation.
- Coronin acts as an inhibitor by maintaining an open conformation.