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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 Katan
Rho 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 Cell

ISSN

1097-2765

Publisher

Elsevier

Issue

2

Volume

34

Page range

223-233

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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