1ajw
From Proteopedia
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'''STRUCTURE OF RHOGDI: A C-TERMINAL BINDING DOMAIN TARGETS AN N-TERMINAL INHIBITORY PEPTIDE TO GTPASES, NMR, 20 STRUCTURES''' | '''STRUCTURE OF RHOGDI: A C-TERMINAL BINDING DOMAIN TARGETS AN N-TERMINAL INHIBITORY PEPTIDE TO GTPASES, NMR, 20 STRUCTURES''' | ||
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[[Category: Gosser, Y Q.]] | [[Category: Gosser, Y Q.]] | ||
[[Category: Rosen, M K.]] | [[Category: Rosen, M K.]] | ||
| - | [[Category: | + | [[Category: Isoprene binding]] |
| - | [[Category: | + | [[Category: Nucleotide exchange]] |
| - | [[Category: | + | [[Category: Rho-gtpase inhibitor]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 10:21:58 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 07:22, 2 May 2008
STRUCTURE OF RHOGDI: A C-TERMINAL BINDING DOMAIN TARGETS AN N-TERMINAL INHIBITORY PEPTIDE TO GTPASES, NMR, 20 STRUCTURES
Overview
The Rho GDP-dissociation inhibitors (GDIs) negatively regulate Rho-family GTPases. The inhibitory activity of GDI derives both from an ability to bind the carboxy-terminal isoprene of Rho family members and extract them from membranes, and from inhibition of GTPase cycling between the GTP- and GDP-bound states. Here we demonstrate that these binding and inhibitory functions of rhoGDI can be attributed to two structurally distinct regions of the protein. A carboxy-terminal folded domain of relative molecular mass 16,000 (M[r] 16K) binds strongly to the Rho-family member Cdc42, yet has little effect on the rate of nucleotide dissociation from the GTPase. The solution structure of this domain shows a beta-sandwich motif with a narrow hydrophobic cleft that binds isoprenes, and an exposed surface that interacts with the protein portion of Cdc42. The amino-terminal region of rhoGDI is unstructured in the absence of target and contributes little to binding, but is necessary to inhibit nucleotide dissociation from Cdc42. These results lead to a model of rhoGDI function in which the carboxy-terminal binding domain targets the amino-terminal inhibitory region to GTPases, resulting in membrane extraction and inhibition of nucleotide cycling.
About this Structure
1AJW is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
Reference
C-terminal binding domain of Rho GDP-dissociation inhibitor directs N-terminal inhibitory peptide to GTPases., Gosser YQ, Nomanbhoy TK, Aghazadeh B, Manor D, Combs C, Cerione RA, Rosen MK, Nature. 1997 Jun 19;387(6635):814-9. PMID:9194563 Page seeded by OCA on Fri May 2 10:21:58 2008
