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Structural Insights into Formation of an Active Signaling Complex between Rac and Phospholipase C Gamma 2
journal contribution
posted on 2023-06-08, 05:27 authored by Tom D Bunney, Olanivi Opaleye, S Mark Roe, Petra Vatter, Rhona W Baxendale, Claudia Walliser, Katy L Everett, Michelle B Josephs, Carolin Christow, Fernando Rodrigues-Lima, Peter Gierschik, Laurence PearlLaurence Pearl, Matilda KatanRho family GTPases are important cellular switches and control a number of physiological functions. Understanding the molecular basis of interaction of these GTPases with their effectors is crucial in understanding their functions in the cell. Here we present the crystal structure of the complex of Rac2 bound to the split pleckstrin homology (spPH) domain of phospholipase C-gamma(2) (PLC gamma(2)). Based on this structure, we illustrate distinct requirements for PLC gamma(2) activation by Rac and EGF and generate Rac effector mutants that specifically block activation of PLC gamma(2), but not the related PLC beta(2) isoform. Furthermore, in addition to the complex, we report the crystal structures of free spPH and Rac2 bound to GDP and GTP gamma S. These structures illustrate a mechanism of conformational switches that accompany formation of signaling active complexes and highlight the role of effector binding as a common feature of Rac and Cdc42 interactions with a variety of effectors.
History
Publication status
- Published
Journal
Molecular CellISSN
1097-2765Publisher
ElsevierExternal DOI
Issue
2Volume
34Page range
223-233Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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