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1htj

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[[Image:1htj.jpg|left|200px]]
[[Image:1htj.jpg|left|200px]]
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{{Structure
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|GENE= KIAA0380 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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{{STRUCTURE_1htj| PDB=1htj | SCENE= }}
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1htj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1htj OCA], [http://www.ebi.ac.uk/pdbsum/1htj PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1htj RCSB]</span>
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'''STRUCTURE OF THE RGS-LIKE DOMAIN FROM PDZ-RHOGEF'''
'''STRUCTURE OF THE RGS-LIKE DOMAIN FROM PDZ-RHOGEF'''
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[[Category: Lewis, M E.]]
[[Category: Lewis, M E.]]
[[Category: Longenecker, K L.]]
[[Category: Longenecker, K L.]]
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[[Category: gef]]
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[[Category: Gef]]
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[[Category: guanine nucleotide exchange factor]]
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[[Category: Guanine nucleotide exchange factor]]
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[[Category: regulator of g protein signaling]]
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[[Category: Regulator of g protein signaling]]
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[[Category: rgs-like]]
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[[Category: Rgs-like]]
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Revision as of 16:13, 2 May 2008

Template:STRUCTURE 1htj

STRUCTURE OF THE RGS-LIKE DOMAIN FROM PDZ-RHOGEF


Overview

BACKGROUND: The multidomain PDZ-RhoGEF is one of many known guanine nucleotide exchange factors that upregulate Rho GTPases. PDZ-RhoGEF and related family members play a critical role in a molecular signaling pathway from heterotrimeric G protein-coupled receptors to Rho proteins. A approximately 200 residue RGS-like (RGSL) domain in PDZ-RhoGEF and its homologs is responsible for the direct association with Galpha12/13 proteins. To better understand structure-function relationships, we initiated crystallographic studies of the RGSL domain from human PDZ-RhoGEF. RESULTS: A recombinant construct of the RGSL domain was expressed in Escherichia coli and purified, but it did not crystallize. Alternative constructs were designed based on a novel strategy of targeting lysine and glutamic acid residues for mutagenesis to alanine. A triple-point mutant functionally identical to the wild-type protein was crystallized, and its structure was determined by the MAD method using Se-methionine (Se-Met) incorporation. A molecular model of the RGSL domain was refined at 2.2 A resolution, revealing an all-helical tertiary fold with the mutations located at intermolecular lattice contacts. CONCLUSIONS: The first nine helices adopt a fold similar to that observed for RGS proteins, although the sequence identity with other such known structures is below 20%. The last three helices are an integral extension of the RGS fold, packing tightly against helices 3 and 4 with multiple hydrophobic interactions. Comparison with RGS proteins suggests features that are likely relevant for interaction with G proteins. Finally, we conclude that the strategy used to produce crystals was beneficial and might be applicable to other proteins resistant to crystallization.

About this Structure

1HTJ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of the RGS-like domain from PDZ-RhoGEF: linking heterotrimeric g protein-coupled signaling to Rho GTPases., Longenecker KL, Lewis ME, Chikumi H, Gutkind JS, Derewenda ZS, Structure. 2001 Jul 3;9(7):559-69. PMID:11470431 Page seeded by OCA on Fri May 2 19:13:03 2008

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