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| | <StructureSection load='6if2' size='340' side='right'caption='[[6if2]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='6if2' size='340' side='right'caption='[[6if2]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6if2]] 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=6IF2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IF2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6if2]] 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=6IF2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IF2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.4Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAB35, RAB1C, RAY ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RUSC2, KIAA0375 ([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=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6if2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6if2 OCA], [http://pdbe.org/6if2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6if2 RCSB], [http://www.ebi.ac.uk/pdbsum/6if2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6if2 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=6if2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6if2 OCA], [https://pdbe.org/6if2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6if2 RCSB], [https://www.ebi.ac.uk/pdbsum/6if2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6if2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/RUSC2_HUMAN RUSC2_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry. | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RAB35_HUMAN RAB35_HUMAN]] The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in the process of endocytosis and is an essential rate-limiting regulator of the fast recycling pathway back to the plasma membrane. During cytokinesis, required for the postfurrowing terminal steps, namely for intercellular bridge stability and abscission, possibly by controlling phosphatidylinositol 4,5-bis phosphate (PIP2) and SEPT2 localization at the intercellular bridge. May indirectly regulate neurite outgrowth.<ref>PMID:16950109</ref> <ref>PMID:21951725</ref> | + | [https://www.uniprot.org/uniprot/RAB35_HUMAN RAB35_HUMAN] The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in the process of endocytosis and is an essential rate-limiting regulator of the fast recycling pathway back to the plasma membrane. During cytokinesis, required for the postfurrowing terminal steps, namely for intercellular bridge stability and abscission, possibly by controlling phosphatidylinositol 4,5-bis phosphate (PIP2) and SEPT2 localization at the intercellular bridge. May indirectly regulate neurite outgrowth.<ref>PMID:16950109</ref> <ref>PMID:21951725</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 6if2" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6if2" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] |
| | + | *[[Ras-related protein Rab 3D structures|Ras-related protein Rab 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lin, L]] | + | [[Category: Lin L]] |
| - | [[Category: Zhang, R]] | + | [[Category: Zhang R]] |
| - | [[Category: Zhu, J]] | + | [[Category: Zhu J]] |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Endocytosis]]
| + | |
| - | [[Category: Rab35]]
| + | |
| - | [[Category: Rusc2]]
| + | |
| Structural highlights
Function
RAB35_HUMAN The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in the process of endocytosis and is an essential rate-limiting regulator of the fast recycling pathway back to the plasma membrane. During cytokinesis, required for the postfurrowing terminal steps, namely for intercellular bridge stability and abscission, possibly by controlling phosphatidylinositol 4,5-bis phosphate (PIP2) and SEPT2 localization at the intercellular bridge. May indirectly regulate neurite outgrowth.[1] [2]
Publication Abstract from PubMed
Rab35, a master regulator of membrane trafficking, regulates diverse cellular processes and is associated with various human diseases. Although a number of effectors have been identified, the molecular basis of Rab35-effector interactions remains unclear. Here, we provide the high-resolution crystal structures of Rab35 in complex with its two specific effectors ACAP2 and RUSC2, respectively. In the Rab35/ACAP2 complex structure, Rab35 binds to the terminal ankyrin repeat and a C-terminal extended alpha helix of ACAP2, revealing a previously uncharacterized binding mode both for Rabs and ankyrin repeats. In the Rab35/RUSC2 complex structure, Arg1015 of RUSC2 functions as a "pseudo-arginine finger" that stabilizes the GTP-bound Rab35, thus facilitating the assembly of Rab35/RUSC2 complex. The structural analysis allows us to design specific Rab35 mutants capable of eliminating Rab35/ACAP2 and Rab35/RUSC2 interactions, but not interfering with other effector bindings. The atomic structures also offer possible explanations to disease-associated mutants identified at the Rab35-effector interfaces.
Rab35/ACAP2 and Rab35/RUSC2 Complex Structures Reveal Molecular Basis for Effector Recognition by Rab35 GTPase.,Lin L, Shi Y, Wang M, Wang C, Zhu J, Zhang R Structure. 2019 Mar 11. pii: S0969-2126(19)30078-4. doi:, 10.1016/j.str.2019.02.008. PMID:30905672[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kouranti I, Sachse M, Arouche N, Goud B, Echard A. Rab35 regulates an endocytic recycling pathway essential for the terminal steps of cytokinesis. Curr Biol. 2006 Sep 5;16(17):1719-25. PMID:16950109 doi:http://dx.doi.org/10.1016/j.cub.2006.07.020
- ↑ Rahajeng J, Giridharan SS, Cai B, Naslavsky N, Caplan S. MICAL-L1 is a tubular endosomal membrane hub that connects Rab35 and Arf6 with Rab8a. Traffic. 2012 Jan;13(1):82-93. doi: 10.1111/j.1600-0854.2011.01294.x. Epub 2011, Oct 24. PMID:21951725 doi:http://dx.doi.org/10.1111/j.1600-0854.2011.01294.x
- ↑ Lin L, Shi Y, Wang M, Wang C, Zhu J, Zhang R. Rab35/ACAP2 and Rab35/RUSC2 Complex Structures Reveal Molecular Basis for Effector Recognition by Rab35 GTPase. Structure. 2019 Mar 11. pii: S0969-2126(19)30078-4. doi:, 10.1016/j.str.2019.02.008. PMID:30905672 doi:http://dx.doi.org/10.1016/j.str.2019.02.008
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