PMID- 10360579
OWN - NLM
STAT- MEDLINE
DCOM- 19990616
LR  - 20110704
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 399
IP  - 6734
DP  - 1999 May 27
TI  - Structure of the small G protein Cdc42 bound to the GTPase-binding domain of ACK.
PG  - 384-8
AB  - The proteins Cdc42 and Rac are members of the Rho family of small GTPases (G
      proteins), which control signal-transduction pathways that lead to rearrangements
      of the cell cytoskeleton, cell differentiation and cell proliferation. They do so
      by binding to downstream effector proteins. Some of these, known as CRIB (for
      Cdc42/Rac interactive-binding) proteins, bind to both Cdc42 and Rac, such as the 
      PAK1-3 serine/threonine kinases, whereas others are specific for Cdc42, such as
      the ACK tyrosine kinases and the Wiscott-Aldrich-syndrome proteins (WASPs). The
      effector loop of Cdc42 and Rac (comprising residues 30-40, also called switch I),
      is one of two regions which change conformation on exchange of GDP for GTP. This 
      region is almost identical in Cdc42 and Racs, indicating that it does not
      determine the specificity of these G proteins. Here we report the solution
      structure of the complex of Cdc42 with the GTPase-binding domain ofACK. Both
      proteins undergo significant conformational changes on binding, to form a new
      type of G-protein/effector complex. The interaction extends the beta-sheet in
      Cdc42 by binding an extended strand from ACK, as seen in Ras/effector
      interactions, but it also involves other regions of the G protein that are
      important for determining the specificity of effector binding.
FAU - Mott, H R
AU  - Mott HR
AD  - Cambridge Centre for Molecular Recognition, Department of Biochemistry,
      University of Cambridge, UK.
FAU - Owen, D
AU  - Owen D
FAU - Nietlispach, D
AU  - Nietlispach D
FAU - Lowe, P N
AU  - Lowe PN
FAU - Manser, E
AU  - Manser E
FAU - Lim, L
AU  - Lim L
FAU - Laue, E D
AU  - Laue ED
LA  - eng
SI  - PDB/1CF4
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 3.6.5.2 (cdc42 GTP-Binding Protein)
SB  - IM
MH  - Amino Acid Sequence
MH  - Cell Cycle Proteins/*chemistry/metabolism
MH  - Conserved Sequence
MH  - Escherichia coli
MH  - GTP Phosphohydrolases/chemistry/metabolism
MH  - GTP-Binding Proteins/*chemistry/metabolism
MH  - Humans
MH  - Magnetic Resonance Spectroscopy
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Protein Binding
MH  - Protein Conformation
MH  - Protein-Tyrosine Kinases/*chemistry/metabolism
MH  - Recombinant Fusion Proteins/chemistry/metabolism
MH  - Sequence Homology, Amino Acid
MH  - cdc42 GTP-Binding Protein
EDAT- 1999/06/09 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/06/09 10:00
PHST- 1999/06/09 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/06/09 10:00 [entrez]
AID - 10.1038/20732 [doi]
PST - ppublish
SO  - Nature. 1999 May 27;399(6734):384-8. doi: 10.1038/20732.