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| | <StructureSection load='6ajl' size='340' side='right'caption='[[6ajl]], [[Resolution|resolution]] 3.23Å' scene=''> | | <StructureSection load='6ajl' size='340' side='right'caption='[[6ajl]], [[Resolution|resolution]] 3.23Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ajl]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AJL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AJL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ajl]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AJL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AJL FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6aj4|6aj4]]</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]] 3.23Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DOCK7, KIAA1771 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CDC42 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6ajl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ajl OCA], [https://pdbe.org/6ajl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ajl RCSB], [https://www.ebi.ac.uk/pdbsum/6ajl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ajl ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ajl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ajl OCA], [http://pdbe.org/6ajl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ajl RCSB], [http://www.ebi.ac.uk/pdbsum/6ajl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ajl ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/DOCK7_HUMAN DOCK7_HUMAN]] Early-onset epileptic encephalopathy-cortical blindness-intellectual disability-facial dysmorphism syndrome. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/DOCK7_HUMAN DOCK7_HUMAN] Early-onset epileptic encephalopathy-cortical blindness-intellectual disability-facial dysmorphism syndrome. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DOCK7_HUMAN DOCK7_HUMAN]] Functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP. Does not have a GEF activity for CDC42. Required for STMN1 'Ser-15' phosphorylation during axon formation and consequently for neuronal polarization (PubMed:16982419). Has a role in pigmentation (By similarity). Involved in the regulation of cortical neurogenesis through the control of radial glial cells (RGCs) proliferation versus differentiation; negatively regulates the basal-to-apical interkinetic nuclear migration of RGCs by antagonizing the microtubule growth-promoting function of TACC3 (By similarity).[UniProtKB:Q8R1A4]<ref>PMID:16982419</ref> [[http://www.uniprot.org/uniprot/CDC42_HUMAN CDC42_HUMAN]] Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase. Plays a role in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia. Mediates CDC42-dependent cell migration.<ref>PMID:14978216</ref> <ref>PMID:15642749</ref> <ref>PMID:17038317</ref> | + | [https://www.uniprot.org/uniprot/DOCK7_HUMAN DOCK7_HUMAN] Functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP. Does not have a GEF activity for CDC42. Required for STMN1 'Ser-15' phosphorylation during axon formation and consequently for neuronal polarization (PubMed:16982419). Has a role in pigmentation (By similarity). Involved in the regulation of cortical neurogenesis through the control of radial glial cells (RGCs) proliferation versus differentiation; negatively regulates the basal-to-apical interkinetic nuclear migration of RGCs by antagonizing the microtubule growth-promoting function of TACC3 (By similarity).[UniProtKB:Q8R1A4]<ref>PMID:16982419</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6ajl" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6ajl" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Dedicator of cytokinesis protein 3D structures|Dedicator of cytokinesis protein 3D structures]] |
| | + | *[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kukimoto-Niino, M]] | + | [[Category: Kukimoto-Niino M]] |
| - | [[Category: Shirouzu, M]] | + | [[Category: Shirouzu M]] |
| - | [[Category: Cdc42]]
| + | |
| - | [[Category: Dhr-2]]
| + | |
| - | [[Category: Dock]]
| + | |
| - | [[Category: Gef]]
| + | |
| - | [[Category: Gtpase]]
| + | |
| - | [[Category: Mutant]]
| + | |
| - | [[Category: Rac]]
| + | |
| - | [[Category: Rho]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Disease
DOCK7_HUMAN Early-onset epileptic encephalopathy-cortical blindness-intellectual disability-facial dysmorphism syndrome. The disease is caused by mutations affecting the gene represented in this entry.
Function
DOCK7_HUMAN Functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP. Does not have a GEF activity for CDC42. Required for STMN1 'Ser-15' phosphorylation during axon formation and consequently for neuronal polarization (PubMed:16982419). Has a role in pigmentation (By similarity). Involved in the regulation of cortical neurogenesis through the control of radial glial cells (RGCs) proliferation versus differentiation; negatively regulates the basal-to-apical interkinetic nuclear migration of RGCs by antagonizing the microtubule growth-promoting function of TACC3 (By similarity).[UniProtKB:Q8R1A4][1]
Publication Abstract from PubMed
The Dedicator Of CytoKinesis (DOCK) family of atypical guanine nucleotide exchange factors activates the Rho family GTPases Rac and/or Cdc42 through DOCK homology region 2 (DHR-2). Previous structural analyses of the DHR-2 domains of DOCK2 and DOCK9 have shown that they preferentially bind Rac1 and Cdc42, respectively; however, the molecular mechanism by which DHR-2 distinguishes between these GTPases is unclear. Here we report the crystal structure of the Cdc42-bound form of the DOCK7 DHR-2 domain showing dual specificity for Rac1 and Cdc42. The structure revealed increased substrate tolerance of DOCK7 at the interfaces with switch 1 and residue 56 of Cdc42. Furthermore, molecular dynamics simulations showed a closed-to-open conformational change in the DOCK7 DHR-2 domain between the Cdc42- and Rac1-bound states by lobe B displacement. Our results suggest that lobe B acts as a sensor for identifying different switch 1 conformations and explain how DOCK7 recognizes both Rac1 and Cdc42.
Structural Basis for the Dual Substrate Specificity of DOCK7 Guanine Nucleotide Exchange Factor.,Kukimoto-Niino M, Tsuda K, Ihara K, Mishima-Tsumagari C, Honda K, Ohsawa N, Shirouzu M Structure. 2019 Feb 16. pii: S0969-2126(19)30045-0. doi:, 10.1016/j.str.2019.02.001. PMID:30853411[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Watabe-Uchida M, John KA, Janas JA, Newey SE, Van Aelst L. The Rac activator DOCK7 regulates neuronal polarity through local phosphorylation of stathmin/Op18. Neuron. 2006 Sep 21;51(6):727-39. PMID:16982419 doi:http://dx.doi.org/S0896-6273(06)00585-X
- ↑ Kukimoto-Niino M, Tsuda K, Ihara K, Mishima-Tsumagari C, Honda K, Ohsawa N, Shirouzu M. Structural Basis for the Dual Substrate Specificity of DOCK7 Guanine Nucleotide Exchange Factor. Structure. 2019 Feb 16. pii: S0969-2126(19)30045-0. doi:, 10.1016/j.str.2019.02.001. PMID:30853411 doi:http://dx.doi.org/10.1016/j.str.2019.02.001
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