8i5f
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8i5f]] is a 4 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=8I5F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8I5F FirstGlance]. <br> | <table><tr><td colspan='2'>[[8i5f]] is a 4 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=8I5F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8I5F FirstGlance]. <br> | ||
| - | </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=8i5f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8i5f OCA], [https://pdbe.org/8i5f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8i5f RCSB], [https://www.ebi.ac.uk/pdbsum/8i5f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8i5f ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</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=8i5f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8i5f OCA], [https://pdbe.org/8i5f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8i5f RCSB], [https://www.ebi.ac.uk/pdbsum/8i5f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8i5f ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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Dedicator of cytokinesis 10 (DOCK10), an evolutionarily conserved guanine nucleotide exchange factor (GEF) for Rho GTPases, has the unique specificity within the DOCK-D subfamily to activate both Cdc42 and Rac, but the structural bases for these activities remained unknown. Here we present the crystal structures of the catalytic DHR2 domain of mouse DOCK10, complexed with either Cdc42 or Rac1. The structures revealed that DOCK10(DHR2) binds to Cdc42 or Rac1 by slightly changing the arrangement of its two catalytic lobes. DOCK10 also has a flexible binding pocket for the 56th GTPase residue, allowing a novel interaction with Trp56(Rac1). The conserved residues in switch 1 of Cdc42 and Rac1 showed common interactions with the unique Lys-His sequence in the beta5/beta6 loop of DOCK10(DHR2). However, the interaction of switch 1 in Rac1 was less stable than that of switch 1 in Cdc42, due to amino acid differences at positions 27 and 30. Structure-based mutagenesis identified the DOCK10 residues that determine the Cdc42/Rac1 dual specificity. | Dedicator of cytokinesis 10 (DOCK10), an evolutionarily conserved guanine nucleotide exchange factor (GEF) for Rho GTPases, has the unique specificity within the DOCK-D subfamily to activate both Cdc42 and Rac, but the structural bases for these activities remained unknown. Here we present the crystal structures of the catalytic DHR2 domain of mouse DOCK10, complexed with either Cdc42 or Rac1. The structures revealed that DOCK10(DHR2) binds to Cdc42 or Rac1 by slightly changing the arrangement of its two catalytic lobes. DOCK10 also has a flexible binding pocket for the 56th GTPase residue, allowing a novel interaction with Trp56(Rac1). The conserved residues in switch 1 of Cdc42 and Rac1 showed common interactions with the unique Lys-His sequence in the beta5/beta6 loop of DOCK10(DHR2). However, the interaction of switch 1 in Rac1 was less stable than that of switch 1 in Cdc42, due to amino acid differences at positions 27 and 30. Structure-based mutagenesis identified the DOCK10 residues that determine the Cdc42/Rac1 dual specificity. | ||
| - | Structural basis for the dual GTPase specificity of the DOCK10 guanine nucleotide exchange factor.,Kukimoto-Niino M, Ihara K, Mishima-Tsumagari C, Inoue M, Fukui Y, Yokoyama S, Shirouzu M Biochem Biophys Res Commun. 2023 | + | Structural basis for the dual GTPase specificity of the DOCK10 guanine nucleotide exchange factor.,Kukimoto-Niino M, Ihara K, Mishima-Tsumagari C, Inoue M, Fukui Y, Yokoyama S, Shirouzu M Biochem Biophys Res Commun. 2023 Apr 23;653:12-20. doi: , 10.1016/j.bbrc.2023.02.054. Epub 2023 Feb 21. PMID:36848820<ref>PMID:36848820</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 8i5f" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 8i5f" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Dedicator of cytokinesis protein 3D structures|Dedicator of cytokinesis protein 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Crystal structure of the DHR-2 domain of DOCK10 in complex with Cdc42 (T17N mutant)
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