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| - | [[Image:1txd.jpg|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1txd| PDB=1txd | SCENE= }} | | {{STRUCTURE_1txd| PDB=1txd | SCENE= }} |
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| - | '''Crystal Structure of the DH/PH domains of Leukemia-associated RhoGEF'''
| + | ===Crystal Structure of the DH/PH domains of Leukemia-associated RhoGEF=== |
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| - | ==Overview==
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| - | Rho guanine-nucleotide exchange factors (RhoGEFs) activate Rho GTPases, and thereby regulate cytoskeletal structure, gene transcription, and cell migration. Leukemia-associated RhoGEF (LARG) belongs to a small subfamily of RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. Herein we describe the atomic structures of the catalytic Dbl homology (DH) and pleckstrin homology (PH) domains of LARG alone and in complex with RhoA. These structures demonstrate that the DH/PH domains of LARG can undergo a dramatic conformational change upon binding RhoA, wherein both the DH and PH domains directly engage RhoA. Through mutational analysis we show that full nucleotide exchange activity requires a novel N-terminal extension on the DH domain that is predicted to exist in a broader family of RhoGEFs that includes p115-RhoGEF, Lbc, Lfc, Net1, and Xpln, and identify regions within the LARG PH domain that contribute to its ability to facilitate nucleotide exchange in vitro. In crystals of the DH/PH-RhoA complex, the active site of RhoA adopts two distinct GDP-excluding conformations among the four unique complexes in the asymmetric unit. Similar changes were previously observed in structures of nucleotide-free Ras and Ef-Tu. A potential protein-docking site on the LARG PH domain is also evident and appears to be conserved throughout the Lbc subfamily of RhoGEFs.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_15331592}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 15331592 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_15331592}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Kristelly, R.]] | | [[Category: Kristelly, R.]] |
| | [[Category: Tesmer, J J.]] | | [[Category: Tesmer, J J.]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:29:02 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 02:15:16 2008'' |
Revision as of 23:15, 28 July 2008
Template:STRUCTURE 1txd
Crystal Structure of the DH/PH domains of Leukemia-associated RhoGEF
Template:ABSTRACT PUBMED 15331592
About this Structure
1TXD is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural determinants of RhoA binding and nucleotide exchange in leukemia-associated Rho guanine-nucleotide exchange factor., Kristelly R, Gao G, Tesmer JJ, J Biol Chem. 2004 Nov 5;279(45):47352-62. Epub 2004 Aug 25. PMID:15331592
Page seeded by OCA on Tue Jul 29 02:15:16 2008
