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| | ==Crystal structure of tetrameric human Rabin8 GEF domain== | | ==Crystal structure of tetrameric human Rabin8 GEF domain== |
| - | <StructureSection load='6f6p' size='340' side='right' caption='[[6f6p]], [[Resolution|resolution]] 2.45Å' scene=''> | + | <StructureSection load='6f6p' size='340' side='right'caption='[[6f6p]], [[Resolution|resolution]] 2.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6f6p]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5oag 5oag]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F6P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6F6P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6f6p]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5oag 5oag]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F6P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6F6P FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAB3IP, RABIN8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 2.45Å</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=6f6p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f6p OCA], [http://pdbe.org/6f6p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f6p RCSB], [http://www.ebi.ac.uk/pdbsum/6f6p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f6p 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=6f6p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f6p OCA], [https://pdbe.org/6f6p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6f6p RCSB], [https://www.ebi.ac.uk/pdbsum/6f6p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6f6p ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RAB3I_HUMAN RAB3I_HUMAN]] Guanine nucleotide exchange factor (GEF) which may activate RAB8A and RAB8B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. Mediates the release of GDP from RAB8A and RAB8B but not from RAB3A or RAB5. Modulates actin organization and promotes polarized transport of RAB8A-specific vesicles to the cell surface. Together with RAB11A, RAB8A, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis.<ref>PMID:12221131</ref> <ref>PMID:20937701</ref> <ref>PMID:20890297</ref> | + | [https://www.uniprot.org/uniprot/RAB3I_HUMAN RAB3I_HUMAN] Guanine nucleotide exchange factor (GEF) which may activate RAB8A and RAB8B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. Mediates the release of GDP from RAB8A and RAB8B but not from RAB3A or RAB5. Modulates actin organization and promotes polarized transport of RAB8A-specific vesicles to the cell surface. Together with RAB11A, RAB8A, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis.<ref>PMID:12221131</ref> <ref>PMID:20937701</ref> <ref>PMID:20890297</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Lorentzen, E]] | + | [[Category: Large Structures]] |
| - | [[Category: Vetter, M]] | + | [[Category: Lorentzen E]] |
| - | [[Category: Gef]] | + | [[Category: Vetter M]] |
| - | [[Category: Guanine nucleotide exchange factor]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Rab3i]]
| + | |
| - | [[Category: Rabin8]]
| + | |
| - | [[Category: Tetramer]]
| + | |
| Structural highlights
Function
RAB3I_HUMAN Guanine nucleotide exchange factor (GEF) which may activate RAB8A and RAB8B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. Mediates the release of GDP from RAB8A and RAB8B but not from RAB3A or RAB5. Modulates actin organization and promotes polarized transport of RAB8A-specific vesicles to the cell surface. Together with RAB11A, RAB8A, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis.[1] [2] [3]
Publication Abstract from PubMed
Rab GTPases and their effectors, activators and guanine nucleotide exchange factors (GEFs) are essential for vesicular transport. Rab8 and its GEF Rabin8 function in formation of the cilium organelle important for developmental signaling and sensory reception. Here we show by size exclusion chromatography and analytical ultracentrifugation that Rabin8 exists in equilibrium between dimers and tetramers. The crystal structure of tetrameric Rabin8 GEF domain reveals an occluded Rab8 binding site suggesting that this oligomer is enzymatically inactive, a notion we verify experimentally using Rabin8/Rab8 GEF assays. We outline a procedure for the purification of active dimeric Rabin8 GEF-domain for in vitro activity assays. This article is protected by copyright. All rights reserved.
Crystal structure of tetrameric human Rabin8 GEF domain.,Vetter M, Boegholm N, Christensen A, Bhogaraju S, Andersen MB, Lorentzen A, Lorentzen E Proteins. 2018 Jan 10. doi: 10.1002/prot.25455. PMID:29318657[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hattula K, Furuhjelm J, Arffman A, Peranen J. A Rab8-specific GDP/GTP exchange factor is involved in actin remodeling and polarized membrane transport. Mol Biol Cell. 2002 Sep;13(9):3268-80. PMID:12221131 doi:http://dx.doi.org/10.1091/mbc.E02-03-0143
- ↑ Yoshimura S, Gerondopoulos A, Linford A, Rigden DJ, Barr FA. Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors. J Cell Biol. 2010 Oct 18;191(2):367-81. doi: 10.1083/jcb.201008051. Epub 2010 Oct, 11. PMID:20937701 doi:http://dx.doi.org/10.1083/jcb.201008051
- ↑ Bryant DM, Datta A, Rodriguez-Fraticelli AE, Peranen J, Martin-Belmonte F, Mostov KE. A molecular network for de novo generation of the apical surface and lumen. Nat Cell Biol. 2010 Nov;12(11):1035-45. doi: 10.1038/ncb2106. Epub 2010 Oct 3. PMID:20890297 doi:10.1038/ncb2106
- ↑ Vetter M, Boegholm N, Christensen A, Bhogaraju S, Andersen MB, Lorentzen A, Lorentzen E. Crystal structure of tetrameric human Rabin8 GEF domain. Proteins. 2018 Jan 10. doi: 10.1002/prot.25455. PMID:29318657 doi:http://dx.doi.org/10.1002/prot.25455
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