This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1ajw
From Proteopedia
(New page: 200px<br /><applet load="1ajw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ajw" /> '''STRUCTURE OF RHOGDI: A C-TERMINAL BINDING DO...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1ajw.jpg|left|200px]]<br /><applet load="1ajw" size=" | + | [[Image:1ajw.jpg|left|200px]]<br /><applet load="1ajw" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ajw" /> | caption="1ajw" /> | ||
'''STRUCTURE OF RHOGDI: A C-TERMINAL BINDING DOMAIN TARGETS AN N-TERMINAL INHIBITORY PEPTIDE TO GTPASES, NMR, 20 STRUCTURES'''<br /> | '''STRUCTURE OF RHOGDI: A C-TERMINAL BINDING DOMAIN TARGETS AN N-TERMINAL INHIBITORY PEPTIDE TO GTPASES, NMR, 20 STRUCTURES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The Rho GDP-dissociation inhibitors (GDIs) negatively regulate Rho-family | + | 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== | ==About this Structure== | ||
| - | 1AJW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http:// | + | 1AJW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AJW OCA]. |
==Reference== | ==Reference== | ||
| Line 13: | Line 13: | ||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Gosser, Y | + | [[Category: Gosser, Y Q.]] |
| - | [[Category: Rosen, M | + | [[Category: Rosen, M K.]] |
[[Category: isoprene binding]] | [[Category: isoprene binding]] | ||
[[Category: nucleotide exchange]] | [[Category: nucleotide exchange]] | ||
[[Category: rho-gtpase inhibitor]] | [[Category: rho-gtpase inhibitor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:45:23 2008'' |
Revision as of 09:45, 21 February 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 Thu Feb 21 11:45:23 2008
