1nty
From Proteopedia
(New page: 200px<br /> <applet load="1nty" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nty, resolution 1.70Å" /> '''Crystal structure o...) |
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caption="1nty, resolution 1.70Å" /> | caption="1nty, resolution 1.70Å" /> | ||
'''Crystal structure of the first DH/PH domain of Trio to 1.7 A'''<br /> | '''Crystal structure of the first DH/PH domain of Trio to 1.7 A'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1NTY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1NTY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NTY OCA]. |
==Reference== | ==Reference== | ||
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[[Category: rho]] | [[Category: rho]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:30:51 2008'' |
Revision as of 14:30, 15 February 2008
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Crystal structure of the first DH/PH domain of Trio to 1.7 A
Contents |
Overview
The multidomain protein Trio regulates among others neuronal outgrowth and, axonal guidance in vertebrates and invertebrates. Trio contains two, Dbl-homology/pleckstrin homology (DH/PH) tandem domains that activate, several RhoGTPases. Here, we present the x-ray structure of the N-terminal, DH/PH, hereafter TrioN, refined to 1.7-A resolution. We show that the, relative orientations of the DH and PH domains of TrioN and free Dbs are, similar. However, this relative orientation is dissimilar to Dbs in the, Dbs/Cdc42 structure. In vitro nucleotide exchange experiments catalyzed by, TrioN show that RhoG is approximately 3x more efficiently exchanged than, Rac and support the conclusion that RhoG is likely the downstream target, of TrioN. Residues 54 and 69, which are not conserved between the two, GTPases, are responsible for this specificity. Dot-blot assay reveals that, the TrioN-PH domain does not detectably bind phosphatidylinositol, 3,4-bisphosphate, PtdIns(3,4)P(2), or other phospholipids. This finding is, supported by our three-dimensional structure and affinity binding, experiments. Interestingly, the presence of RhoG but not Rac or a, C-terminal-truncated RhoG mutant allows TrioN to bind PtdIns(3,4)P(2) with, a micromolar affinity constant. We conclude the variable C-terminal basic, tail of RhoG specifically assists the recruitment of the TrioN-PH domain, to specific membrane-bound phospholipids. Our data suggest a role for the, phosphoinositide 3-kinase, PI 3-kinase, in modulating the Trio/RhoG, signaling pathway.
Disease
Known disease associated with this structure: Deafness, autosomal recessive 28 OMIM:[609761]
About this Structure
1NTY is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The C-terminal basic tail of RhoG assists the guanine nucleotide exchange factor trio in binding to phospholipids., Skowronek KR, Guo F, Zheng Y, Nassar N, J Biol Chem. 2004 Sep 3;279(36):37895-907. Epub 2004 Jun 15. PMID:15199069
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