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| | ==Crystal structure of GTP-bound Rab8:Rabin8== | | ==Crystal structure of GTP-bound Rab8:Rabin8== |
| - | <StructureSection load='4lhz' size='340' side='right' caption='[[4lhz]], [[Resolution|resolution]] 3.20Å' scene=''> | + | <StructureSection load='4lhz' size='340' side='right'caption='[[4lhz]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4lhz]] is a 6 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=4LHZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LHZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4lhz]] is a 6 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=4LHZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LHZ 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></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]] 3.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lhv|4lhv]], [[4lhw|4lhw]], [[4lhx|4lhx]], [[4lhy|4lhy]], [[4li0|4li0]]</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></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAB8A, MEL, RAB8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RAB3IP, RABIN8 ([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=4lhz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lhz OCA], [https://pdbe.org/4lhz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lhz RCSB], [https://www.ebi.ac.uk/pdbsum/4lhz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lhz 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=4lhz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lhz OCA], [http://pdbe.org/4lhz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lhz RCSB], [http://www.ebi.ac.uk/pdbsum/4lhz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lhz ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RAB8A_HUMAN RAB8A_HUMAN]] May be involved in vesicular trafficking and neurotransmitter release. Together with RAB11A, RAB3IP, 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. Together with MYO5B and RAB11A participates in epithelial cell polarization.<ref>PMID:20890297</ref> <ref>PMID:21282656</ref> [[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/RAB8A_HUMAN RAB8A_HUMAN] May be involved in vesicular trafficking and neurotransmitter release. Together with RAB11A, RAB3IP, 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. Together with MYO5B and RAB11A participates in epithelial cell polarization.<ref>PMID:20890297</ref> <ref>PMID:21282656</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: Goody, R S]] | + | [[Category: Large Structures]] |
| - | [[Category: Guo, Z]] | + | [[Category: Goody RS]] |
| - | [[Category: Hou, X M]] | + | [[Category: Guo Z]] |
| - | [[Category: Itzen, A]] | + | [[Category: Hou XM]] |
| - | [[Category: Guanine nucleotide exchange factor]] | + | [[Category: Itzen A]] |
| - | [[Category: Protein transport]]
| + | |
| - | [[Category: Small gtpase]]
| + | |
| Structural highlights
Function
RAB8A_HUMAN May be involved in vesicular trafficking and neurotransmitter release. Together with RAB11A, RAB3IP, 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. Together with MYO5B and RAB11A participates in epithelial cell polarization.[1] [2]
Publication Abstract from PubMed
Small G-proteins (G) of the Ras-superfamily control the temporal and spatial coordination of intracellular signaling networks by acting as molecular on/off switches. Guanine nucleotide exchange factors (GEFs) regulate the activation of these G-proteins through catalytic replace-ment of guanosine diphosphate (GDP) by gua-nosine triphosphate (GTP). During nucleotide exchange, three distinct substrate-enzyme complexes occur: A ternary complex with GDP at the start of reaction (G:GDP:GEF), an intermediary nucleotide-free binary complex (G:GEF), and a ternary GTP-complex after productive G-protein activation (G:GTP:GEF). Here we show structural snapshots of the full nucleotide-exchange reaction sequence together with the G-protein substrates and products using Rabin8/GRAB (GEF) and Rab8 (G-protein) as a model system. Together with a thorough enzymatic characterization, our data provide a detailed view into the mechanism of Rabin8/GRAB mediated nucleotide exchange.
Intermediates in the Guanine Nucleotide Exchange Reaction of Rab8 Catalyzed by Rabin8/GRAB.,Guo Z, Hou X, Goody RS, Itzen A J Biol Chem. 2013 Sep 26. PMID:24072714[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ Roland JT, Bryant DM, Datta A, Itzen A, Mostov KE, Goldenring JR. Rab GTPase-Myo5B complexes control membrane recycling and epithelial polarization. Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2789-94. doi:, 10.1073/pnas.1010754108. Epub 2011 Jan 31. PMID:21282656 doi:10.1073/pnas.1010754108
- ↑ Guo Z, Hou X, Goody RS, Itzen A. Intermediates in the Guanine Nucleotide Exchange Reaction of Rab8 Catalyzed by Rabin8/GRAB. J Biol Chem. 2013 Sep 26. PMID:24072714 doi:http://dx.doi.org/10.1074/jbc.M113.498329
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