7clx

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Current revision (10:51, 27 March 2024) (edit) (undo)
 
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<StructureSection load='7clx' size='340' side='right'caption='[[7clx]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
<StructureSection load='7clx' size='340' side='right'caption='[[7clx]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[7clx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CLX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CLX FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7clx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CLX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CLX FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7cly|7cly]]</div></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Dock8 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7clx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7clx OCA], [https://pdbe.org/7clx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7clx RCSB], [https://www.ebi.ac.uk/pdbsum/7clx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7clx ProSAT]</span></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=7clx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7clx OCA], [https://pdbe.org/7clx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7clx RCSB], [https://www.ebi.ac.uk/pdbsum/7clx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7clx ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/DOCK8_MOUSE DOCK8_MOUSE]] Potential guanine nucleotide exchange factor (GEF). GEF proteins activate some small GTPases by exchanging bound GDP for free GTP (By similarity).
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[https://www.uniprot.org/uniprot/DOCK8_MOUSE DOCK8_MOUSE] Potential guanine nucleotide exchange factor (GEF). GEF proteins activate some small GTPases by exchanging bound GDP for free GTP (By similarity).
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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DOCK8 is a Cdc42-specific guanine-nucleotide exchange factor that is essential for development and functions of various subsets of leukocytes in innate and acquired immune responses. Although DOCK8 plays a critical role in spatial control of Cdc42 activity during interstitial leukocyte migration, the mechanism remains unclear. We show that the DOCK homology region (DHR)-1 domain of DOCK8 binds specifically to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and is required for its recruitment to the plasma membrane. Structural and biochemical analyses reveal that DOCK8 DHR-1 domain consists of a C2 domain-like core with loops creating the upper surface pocket, where three basic residues are located for stereospecific recognition of phosphoinositides. Substitution of the two basic residues, K576 and R581, with alanine abolished PI(4,5)P2 binding in vitro, ablated the ability of DOCK8 to activate Cdc42 and support leukocyte migration in three-dimensional collagen gels. Dendritic cells carrying the mutation exhibited defective interstitial migration in vivo. Thus, our study uncovers a critical role of DOCK8 in coupling PI(4,5)P2 signaling with Cdc42 activation for immune regulation.
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A conserved PI(4,5)P2-binding domain is critical for immune regulatory function of DOCK8.,Sakurai T, Kukimoto-Niino M, Kunimura K, Yamane N, Sakata D, Aihara R, Yasuda T, Yokoyama S, Shirouzu M, Fukui Y, Uruno T Life Sci Alliance. 2021 Feb 11;4(4). pii: 4/4/e202000873. doi:, 10.26508/lsa.202000873. Print 2021 Apr. PMID:33574036<ref>PMID:33574036</ref>
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==See Also==
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*[[Dedicator of cytokinesis protein 3D structures|Dedicator of cytokinesis protein 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7clx" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Lk3 transgenic mice]]
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[[Category: Mus musculus]]
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[[Category: Fukui, Y]]
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[[Category: Fukui Y]]
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[[Category: Kukimoto-Niino, M]]
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[[Category: Kukimoto-Niino M]]
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[[Category: Shirouzu, M]]
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[[Category: Shirouzu M]]
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[[Category: Uruno, T]]
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[[Category: Uruno T]]
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[[Category: Yokoyama, S]]
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[[Category: Yokoyama S]]
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[[Category: Cdc42]]
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[[Category: Dock]]
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[[Category: Guanine nucleotide exchange factor]]
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[[Category: Membrane]]
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[[Category: Phosphoinositide]]
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[[Category: Rho gtpase]]
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[[Category: Signaling protein]]
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Current revision

Crystal structure of the DOCK8 DHR-1 domain

PDB ID 7clx

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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