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< | ==Crystal Structure of the Dbl and Pleckstrin homology domains of Dbs in complex with RhoA== | ||
<StructureSection load='1lb1' size='340' side='right'caption='[[1lb1]], [[Resolution|resolution]] 2.81Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1lb1]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LB1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LB1 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.81Å</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1lb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lb1 OCA], [https://pdbe.org/1lb1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lb1 RCSB], [https://www.ebi.ac.uk/pdbsum/1lb1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lb1 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/MCF2L_MOUSE MCF2L_MOUSE] Guanine nucleotide exchange factor that potentially links pathways that signal through RAC1, RHOA and CDC42. Catalyzes guanine nucleotide exchange on RHOA and CDC42 and interacts specifically with the GTP-bound form of RAC1, suggesting that it functions as an effector of RAC1. May also participate in axonal transport in the brain. Becomes activated and highly tumorigenic by truncation of the N-terminus (By similarity). | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lb/1lb1_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1lb1 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Activation of Rho-family GTPases involves the removal of bound GDP and the subsequent loading of GTP, all catalyzed by guanine nucleotide exchange factors (GEFs) of the Dbl-family. Despite high sequence conservation among Rho GTPases, Dbl proteins possess a wide spectrum of discriminatory potentials for Rho-family members. To rationalize this specificity, we have determined crystal structures of the conserved, catalytic fragments (Dbl and pleckstrin homology domains) of the exchange factors intersectin and Dbs in complex with their cognate GTPases, Cdc42 and RhoA, respectively. Structure-based mutagenesis of intersectin and Dbs reveals the key determinants responsible for promoting exchange activity in Cdc42, Rac1 and RhoA. These findings provide critical insight into the structural features necessary for the proper pairing of Dbl-exchange factors with Rho GTPases and now allow for the detailed manipulation of signaling pathways mediated by these oncoproteins in vivo. | |||
Structural basis for the selective activation of Rho GTPases by Dbl exchange factors.,Snyder JT, Worthylake DK, Rossman KL, Betts L, Pruitt WM, Siderovski DP, Der CJ, Sondek J Nat Struct Biol. 2002 Jun;9(6):468-75. PMID:12006984<ref>PMID:12006984</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1lb1" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Rho GTPase 3D structures|Rho GTPase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
== | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Betts L]] | |||
[[Category: Betts | [[Category: Der CJ]] | ||
[[Category: Der | [[Category: Pruitt WM]] | ||
[[Category: Pruitt | [[Category: Rossman KL]] | ||
[[Category: Rossman | [[Category: Siderovski DP]] | ||
[[Category: Siderovski | [[Category: Snyder JT]] | ||
[[Category: Snyder | [[Category: Sondek J]] | ||
[[Category: Sondek | [[Category: Worthylake DK]] | ||
[[Category: Worthylake | |||
Latest revision as of 12:11, 16 August 2023
Crystal Structure of the Dbl and Pleckstrin homology domains of Dbs in complex with RhoACrystal Structure of the Dbl and Pleckstrin homology domains of Dbs in complex with RhoA
Structural highlights
FunctionMCF2L_MOUSE Guanine nucleotide exchange factor that potentially links pathways that signal through RAC1, RHOA and CDC42. Catalyzes guanine nucleotide exchange on RHOA and CDC42 and interacts specifically with the GTP-bound form of RAC1, suggesting that it functions as an effector of RAC1. May also participate in axonal transport in the brain. Becomes activated and highly tumorigenic by truncation of the N-terminus (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedActivation of Rho-family GTPases involves the removal of bound GDP and the subsequent loading of GTP, all catalyzed by guanine nucleotide exchange factors (GEFs) of the Dbl-family. Despite high sequence conservation among Rho GTPases, Dbl proteins possess a wide spectrum of discriminatory potentials for Rho-family members. To rationalize this specificity, we have determined crystal structures of the conserved, catalytic fragments (Dbl and pleckstrin homology domains) of the exchange factors intersectin and Dbs in complex with their cognate GTPases, Cdc42 and RhoA, respectively. Structure-based mutagenesis of intersectin and Dbs reveals the key determinants responsible for promoting exchange activity in Cdc42, Rac1 and RhoA. These findings provide critical insight into the structural features necessary for the proper pairing of Dbl-exchange factors with Rho GTPases and now allow for the detailed manipulation of signaling pathways mediated by these oncoproteins in vivo. Structural basis for the selective activation of Rho GTPases by Dbl exchange factors.,Snyder JT, Worthylake DK, Rossman KL, Betts L, Pruitt WM, Siderovski DP, Der CJ, Sondek J Nat Struct Biol. 2002 Jun;9(6):468-75. PMID:12006984[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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