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9ltp
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human RAB43 in GDP-AlF3 transition state complex with USP6NL TBC domain== | |
| + | <StructureSection load='9ltp' size='340' side='right'caption='[[9ltp]], [[Resolution|resolution]] 2.49Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9ltp]] is a 4 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=9LTP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9LTP FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.49Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AF3:ALUMINUM+FLUORIDE'>AF3</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></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=9ltp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ltp OCA], [https://pdbe.org/9ltp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ltp RCSB], [https://www.ebi.ac.uk/pdbsum/9ltp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ltp ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/US6NL_HUMAN US6NL_HUMAN] Acts as a GTPase-activating protein for RAB5A and RAB43. Involved in receptor trafficking. In complex with EPS8 inhibits internalization of EGFR. Involved in retrograde transport from the endocytic pathway to the Golgi apparatus. Involved in the transport of Shiga toxin from early and recycling endosomes to the trans-Golgi network. Required for structural integrity of the Golgi complex.<ref>PMID:11099046</ref> <ref>PMID:17562788</ref> <ref>PMID:17684057</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | TBC domain-containing Rab GTPase-activating proteins (TBCs) play key roles in regulating intracellular trafficking, and mutations in these proteins can disrupt Rab inactivation and contribute to human disease. However, the molecular principles governing the substrate specificity of TBCs remain poorly understood. Here, we delineate the molecular mechanism by which RN-Tre (also known as USP6NL), an RQ-dual finger TBC protein, selectively recognizes and inactivates Rab43. The crystal structure of the RN-Tre-Rab43 complex reveals a bipartite recognition mechanism: the N-terminal subdomain catalytically remodels Rab43 Switch regions, while the C-terminal subdomain engages Switch II and reorients the hydrophobic triad to confer specificity. Structural and mutational analyses identify Leu146 and several C-terminal residues as key determinants of RN-Tre specificity, which lead us to identify Rab19 as an additional substrate. Functional assays demonstrate that disease-associated RN-Tre mutations impair GAP activity, resulting in aberrant Golgi architecture and endocytic trafficking. Collectively, this study establishes a general structural paradigm for substrate discrimination by TBCs and highlights their pivotal roles in membrane trafficking and disease. | ||
| - | + | Molecular basis of Rab43 inactivation by RN-Tre in endocytic trafficking unveils a general Rab-GAP recognition mechanism.,Wang J, Liu T, Zhang Z, Yan W Int J Biol Macromol. 2025 Dec 14;338(Pt 1):149561. doi: , 10.1016/j.ijbiomac.2025.149561. PMID:41401861<ref>PMID:41401861</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 9ltp" style="background-color:#fffaf0;"></div> |
| - | [[Category: Wang | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Wang J]] | ||
| + | [[Category: Yan WP]] | ||
Current revision
Crystal structure of human RAB43 in GDP-AlF3 transition state complex with USP6NL TBC domain
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