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| | ==Structural basis of membrane-targeting by Dock180== | | ==Structural basis of membrane-targeting by Dock180== |
| - | <StructureSection load='3l4c' size='340' side='right' caption='[[3l4c]], [[Resolution|resolution]] 2.37Å' scene=''> | + | <StructureSection load='3l4c' size='340' side='right'caption='[[3l4c]], [[Resolution|resolution]] 2.37Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3l4c]] is a 2 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=3L4C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3L4C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3l4c]] is a 2 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=3L4C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3L4C FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene></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]] 2.37Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DOCK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene></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=3l4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l4c OCA], [http://pdbe.org/3l4c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3l4c RCSB], [http://www.ebi.ac.uk/pdbsum/3l4c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3l4c 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=3l4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l4c OCA], [https://pdbe.org/3l4c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3l4c RCSB], [https://www.ebi.ac.uk/pdbsum/3l4c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3l4c ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DOCK1_HUMAN DOCK1_HUMAN]] Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Functions as a guanine nucleotide exchange factor (GEF), which activates Rac Rho small GTPases by exchanging bound GDP for free GTP. Its GEF activity may be enhanced by ELMO1.<ref>PMID:8657152</ref> | + | [https://www.uniprot.org/uniprot/DOCK1_HUMAN DOCK1_HUMAN] Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Functions as a guanine nucleotide exchange factor (GEF), which activates Rac Rho small GTPases by exchanging bound GDP for free GTP. Its GEF activity may be enhanced by ELMO1.<ref>PMID:8657152</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3l4c" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3l4c" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Dedicator of cytokinesis protein 3D structures|Dedicator of cytokinesis protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bankston, L A]] | + | [[Category: Large Structures]] |
| - | [[Category: Bobkov, A A]] | + | [[Category: Bankston LA]] |
| - | [[Category: Cote, J F]] | + | [[Category: Bobkov AA]] |
| - | [[Category: Jaroszewski, L]] | + | [[Category: Cote J-F]] |
| - | [[Category: Liddington, R C]] | + | [[Category: Jaroszewski L]] |
| - | [[Category: Patel, M]] | + | [[Category: Liddington RC]] |
| - | [[Category: Premkumar, L]] | + | [[Category: Patel M]] |
| - | [[Category: Stec, B]] | + | [[Category: Premkumar L]] |
| - | [[Category: Vuori, K]] | + | [[Category: Stec B]] |
| - | [[Category: Apoptosis]]
| + | [[Category: Vuori K]] |
| - | [[Category: Cell adhesion]]
| + | |
| - | [[Category: Cell invasion]]
| + | |
| - | [[Category: Cell migration]]
| + | |
| - | [[Category: Cell polarity]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Cytoskeleton]]
| + | |
| - | [[Category: Dock1]]
| + | |
| - | [[Category: Dock180]]
| + | |
| - | [[Category: Guanine exchange factor]]
| + | |
| - | [[Category: Guanine-nucleotide releasing factor]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Phagocytosis]]
| + | |
| - | [[Category: Phosphoinositide specificity]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Rho gtpase]]
| + | |
| - | [[Category: Sh3 domain]]
| + | |
| - | [[Category: Sh3-binding]]
| + | |
| Structural highlights
Function
DOCK1_HUMAN Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Functions as a guanine nucleotide exchange factor (GEF), which activates Rac Rho small GTPases by exchanging bound GDP for free GTP. Its GEF activity may be enhanced by ELMO1.[1]
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 PubMed
The Dock180 family of atypical Rho family guanine nucleotide exchange factors (Rho-GEFs) regulate a variety of processes involving cellular or subcellular polarization, including cell migration and phagocytosis. Each contains a Dock homology region-1 (DHR-1) domain that is required to localize its GEF activity to a specific membrane compartment where levels of phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P(3)) are up-regulated by the local activity of PtdIns 3-kinase. Here we define the structural and energetic bases of phosphoinositide specificity by the DHR-1 domain of Dock1 (a GEF for Rac1), and show that DHR-1 utilizes a C2 domain scaffold and surface loops to create a basic pocket on its upper surface for recognition of the PtdIns(3,4,5)P(3) head group. The pocket has many of the characteristics of those observed in pleckstrin homology domains. We show that point mutations in the pocket that abolish phospholipid binding in vitro ablate the ability of Dock1 to induce cell polarization, and propose a model that brings together recent mechanistic and structural studies to rationalize the central role of DHR-1 in dynamic membrane targeting of the Rho-GEF activity of Dock180.
Structural basis of membrane targeting by the Dock180 family of Rho family guanine exchange factors (Rho-GEFs).,Premkumar L, Bobkov AA, Patel M, Jaroszewski L, Bankston LA, Stec B, Vuori K, Cote JF, Liddington RC J Biol Chem. 2010 Apr 23;285(17):13211-22. Epub 2010 Feb 18. PMID:20167601[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hasegawa H, Kiyokawa E, Tanaka S, Nagashima K, Gotoh N, Shibuya M, Kurata T, Matsuda M. DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane. Mol Cell Biol. 1996 Apr;16(4):1770-6. PMID:8657152
- ↑ Premkumar L, Bobkov AA, Patel M, Jaroszewski L, Bankston LA, Stec B, Vuori K, Cote JF, Liddington RC. Structural basis of membrane targeting by the Dock180 family of Rho family guanine exchange factors (Rho-GEFs). J Biol Chem. 2010 Apr 23;285(17):13211-22. Epub 2010 Feb 18. PMID:20167601 doi:10.1074/jbc.M110.102517
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