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| | ==Crystal structure of human rab1b bound to GDP and BEF3 in complex with the GAP domain of TBC1D20 from homo sapiens== | | ==Crystal structure of human rab1b bound to GDP and BEF3 in complex with the GAP domain of TBC1D20 from homo sapiens== |
| - | <StructureSection load='4hlq' size='340' side='right' caption='[[4hlq]], [[Resolution|resolution]] 3.30Å' scene=''> | + | <StructureSection load='4hlq' size='340' side='right'caption='[[4hlq]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4hlq]] is a 10 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=4HLQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HLQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4hlq]] is a 10 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=4HLQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HLQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BEF:BERYLLIUM+TRIFLUORIDE+ION'>BEF</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEF:BERYLLIUM+TRIFLUORIDE+ION'>BEF</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hl4|4hl4]]</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=4hlq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hlq OCA], [https://pdbe.org/4hlq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hlq RCSB], [https://www.ebi.ac.uk/pdbsum/4hlq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hlq ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TBC1D20, C20orf140 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RAB1B ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4hlq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hlq OCA], [http://pdbe.org/4hlq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hlq RCSB], [http://www.ebi.ac.uk/pdbsum/4hlq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hlq ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/TBC20_HUMAN TBC20_HUMAN]] Micro syndrome. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/TBC20_HUMAN TBC20_HUMAN] Micro syndrome. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TBC20_HUMAN TBC20_HUMAN]] GTPase-activating protein specific for Rab1 and Rab2 small GTPase families for which it can accelerate the intrinsic GTP hydrolysis rate by more than five orders of magnitude. [[http://www.uniprot.org/uniprot/RAB1B_HUMAN RAB1B_HUMAN]] Protein transport. Regulates vesicular transport between the endoplasmic reticulum and successive Golgi compartments.<ref>PMID:9437002</ref> | + | [https://www.uniprot.org/uniprot/TBC20_HUMAN TBC20_HUMAN] GTPase-activating protein specific for Rab1 and Rab2 small GTPase families for which it can accelerate the intrinsic GTP hydrolysis rate by more than five orders of magnitude. |
| | <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: Gavriljuk, K]] | + | [[Category: Large Structures]] |
| - | [[Category: Gazdag, E M]] | + | [[Category: Gavriljuk K]] |
| - | [[Category: Gerwert, K]] | + | [[Category: Gazdag EM]] |
| - | [[Category: Goody, R S]] | + | [[Category: Gerwert K]] |
| - | [[Category: Itzen, A]] | + | [[Category: Goody RS]] |
| - | [[Category: Koetting, C]] | + | [[Category: Itzen A]] |
| - | [[Category: Fluoride]]
| + | [[Category: Koetting C]] |
| - | [[Category: Gtpase-activating protein]]
| + | |
| - | [[Category: Hydrolase activator-protein transport complex]]
| + | |
| - | [[Category: Rab gtp-binding protein]]
| + | |
| - | [[Category: Rab1b]]
| + | |
| - | [[Category: Rabgap]]
| + | |
| Structural highlights
Disease
TBC20_HUMAN Micro syndrome. The disease is caused by mutations affecting the gene represented in this entry.
Function
TBC20_HUMAN GTPase-activating protein specific for Rab1 and Rab2 small GTPase families for which it can accelerate the intrinsic GTP hydrolysis rate by more than five orders of magnitude.
Publication Abstract from PubMed
Rab GTPases, key regulators of vesicular transport, hydrolyze GTP very slowly unless assisted by Rab GTPase-activating proteins (RabGAPs). Dysfunction of RabGAPs is involved in many diseases. By combining X-ray structure analysis and time-resolved FTIR spectroscopy we reveal here the detailed molecular reaction mechanism of a complex between human Rab and RabGAP at the highest possible spatiotemporal resolution and in atomic detail. A glutamine residue of Rab proteins (cis-glutamine) that is essential for intrinsic activity is less important in the GAP-activated reaction. During generation of the RabGAP.Rab:GTP complex, there is a rapid conformational change in which the cis-glutamine is replaced by a glutamine from RabGAP (trans-glutamine); this differs from the RasGAP mechanism, where the cis-glutamine is also important for GAP catalysis. However, as in the case of Ras, a trans-arginine is also recruited to complete the active center during this conformational change. In contrast to the RasGAP mechanism, an accumulation of a state in which phosphate is bound is not observed, and bond breakage is the rate-limiting step. The movement of trans-glutamine and trans-arginine into the catalytic site and bond breakage during hydrolysis are monitored in real time. The combination of X-ray structure analysis and time-resolved FTIR spectroscopy provides detailed insight in the catalysis of human Rab GTPases.
Catalytic mechanism of a mammalian Rab{middle dot}RabGAP complex in atomic detail.,Gavriljuk K, Gazdag EM, Itzen A, Kotting C, Goody RS, Gerwert K Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21348-53. doi:, 10.1073/pnas.1214431110. Epub 2012 Dec 12. PMID:23236136[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gavriljuk K, Gazdag EM, Itzen A, Kotting C, Goody RS, Gerwert K. Catalytic mechanism of a mammalian Rab{middle dot}RabGAP complex in atomic detail. Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21348-53. doi:, 10.1073/pnas.1214431110. Epub 2012 Dec 12. PMID:23236136 doi:http://dx.doi.org/10.1073/pnas.1214431110
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