PMID- 19394299
OWN - NLM
STAT- MEDLINE
DCOM- 20090622
LR  - 20231213
IS  - 1097-4164 (Electronic)
IS  - 1097-2765 (Linking)
VI  - 34
IP  - 2
DP  - 2009 Apr 24
TI  - Structural insights into formation of an active signaling complex between Rac and 
      phospholipase C gamma 2.
PG  - 223-33
LID - 10.1016/j.molcel.2009.02.023 [doi]
AB  - 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) 
      (PLCgamma(2)). Based on this structure, we illustrate distinct requirements for 
      PLCgamma(2) activation by Rac and EGF and generate Rac effector mutants that 
      specifically block activation of PLCgamma(2), but not the related PLCbeta(2) 
      isoform. Furthermore, in addition to the complex, we report the crystal 
      structures of free spPH and Rac2 bound to GDP and GTPgammaS. 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.
FAU - Bunney, Tom D
AU  - Bunney TD
AD  - Section of Cell and Molecular Biology , The Institute of Cancer Research, London, 
      UK. tom.bunney@icr.ac.uk
FAU - Opaleye, Olaniyi
AU  - Opaleye O
FAU - Roe, S Mark
AU  - Roe SM
FAU - Vatter, Petra
AU  - Vatter P
FAU - Baxendale, Rhona W
AU  - Baxendale RW
FAU - Walliser, Claudia
AU  - Walliser C
FAU - Everett, Katy L
AU  - Everett KL
FAU - Josephs, Michelle B
AU  - Josephs MB
FAU - Christow, Carolin
AU  - Christow C
FAU - Rodrigues-Lima, Fernando
AU  - Rodrigues-Lima F
FAU - Gierschik, Peter
AU  - Gierschik P
FAU - Pearl, Laurence H
AU  - Pearl LH
FAU - Katan, Matilda
AU  - Katan M
LA  - eng
SI  - PDB/2W2T
SI  - PDB/2W2V
SI  - PDB/2W2W
SI  - PDB/2W2X
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell
JT  - Molecular cell
JID - 9802571
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 3.1.4.3 (Phospholipase C gamma)
RN  - EC 3.6.5.2 (rac GTP-Binding Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Crystallography, X-Ray
MH  - Enzyme Activation
MH  - Epidermal Growth Factor/metabolism
MH  - Humans
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Phospholipase C gamma/*chemistry/metabolism
MH  - Protein Interaction Mapping
MH  - Protein Structure, Tertiary
MH  - Sequence Alignment
MH  - Substrate Specificity
MH  - Thermodynamics
MH  - rac GTP-Binding Proteins/*chemistry/metabolism
MH  - RAC2 GTP-Binding Protein
EDAT- 2009/04/28 09:00
MHDA- 2009/06/23 09:00
CRDT- 2009/04/28 09:00
PHST- 2008/12/18 00:00 [received]
PHST- 2009/01/28 00:00 [revised]
PHST- 2009/02/20 00:00 [accepted]
PHST- 2009/04/28 09:00 [entrez]
PHST- 2009/04/28 09:00 [pubmed]
PHST- 2009/06/23 09:00 [medline]
AID - S1097-2765(09)00139-7 [pii]
AID - 10.1016/j.molcel.2009.02.023 [doi]
PST - ppublish
SO  - Mol Cell. 2009 Apr 24;34(2):223-33. doi: 10.1016/j.molcel.2009.02.023.