2nz8
From Proteopedia
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| - | [[Image:2nz8.gif|left|200px]] | + | [[Image:2nz8.gif|left|200px]] |
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| - | '''N-terminal DHPH cassette of Trio in complex with nucleotide-free Rac1''' | + | {{Structure |
| + | |PDB= 2nz8 |SIZE=350|CAPTION= <scene name='initialview01'>2nz8</scene>, resolution 2.000Å | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= | ||
| + | |GENE= RAC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), TRIO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''N-terminal DHPH cassette of Trio in complex with nucleotide-free Rac1''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2NZ8 is a [ | + | 2NZ8 is a [[Protein complex]] structure of sequences 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=2NZ8 OCA]. |
==Reference== | ==Reference== | ||
| - | The DH and PH domains of Trio coordinately engage Rho GTPases for their efficient activation., Chhatriwala MK, Betts L, Worthylake DK, Sondek J, J Mol Biol. 2007 May 18;368(5):1307-20. Epub 2007 Feb 22. PMID:[http:// | + | The DH and PH domains of Trio coordinately engage Rho GTPases for their efficient activation., Chhatriwala MK, Betts L, Worthylake DK, Sondek J, J Mol Biol. 2007 May 18;368(5):1307-20. Epub 2007 Feb 22. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17391702 17391702] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: trio; rac1; dbl-family gef; rho-family gtpase; dh/ph cassette]] | [[Category: trio; rac1; dbl-family gef; rho-family gtpase; dh/ph cassette]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:53:05 2008'' |
Revision as of 15:53, 20 March 2008
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| , resolution 2.000Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | RAC1 (Homo sapiens), TRIO (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
N-terminal DHPH cassette of Trio in complex with nucleotide-free Rac1
Contents |
Overview
Rho-family GTPases are activated by the exchange of bound GDP for GTP, a process that is catalyzed by Dbl-family guanine nucleotide exchange factors (GEFs). The catalytic unit of Dbl-family GEFs consists of a Dbl homology (DH) domain followed almost invariantly by a pleckstrin-homology (PH) domain. The majority of the catalytic interface forms between the switch regions of the GTPase and the DH domain, but full catalytic activity often requires the associated PH domain. Although PH domains are usually characterized as lipid-binding regions, they also participate in protein-protein interactions. For example, the DH-associated PH domain of Dbs must contact its cognate GTPases for efficient exchange. Similarly, the N-terminal DH/PH fragment of Trio, which catalyzes exchange on both Rac1 and RhoG, is fourfold more active in vitro than the isolated DH domain. Given continued uncertainty regarding functional roles of DH-associated PH domains, we have undertaken structural and functional analyses of the N-terminal DH/PH cassette of Trio. The crystal structure of this fragment of Trio bound to nucleotide-depleted Rac1 highlights the engagement of the PH domain with Rac1 and substitution of residues involved in this interface substantially diminishes activation of Rac1 and RhoG. Also, these mutations significantly reduce the ability of full-length Trio to induce neurite outgrowth dependent on RhoG activation in PC-12 cells. Overall, these studies substantiate a general role for DH-associated PH domains in engaging Rho GTPases directly for efficient guanine nucleotide exchange and support a parsimonious explanation for the essentially invariant linkage between DH and PH domains.
Disease
Known disease associated with this structure: Deafness, autosomal recessive 28 OMIM:[609761]
About this Structure
2NZ8 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The DH and PH domains of Trio coordinately engage Rho GTPases for their efficient activation., Chhatriwala MK, Betts L, Worthylake DK, Sondek J, J Mol Biol. 2007 May 18;368(5):1307-20. Epub 2007 Feb 22. PMID:17391702
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