View source for 9ltq


==Crystal structure of human RAB43 in complex with GppNHp==
<StructureSection load='9ltq' size='340' side='right'caption='[[9ltq]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9ltq]] 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=9LTQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9LTQ 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]] 1.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</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'>[https://proteopedia.org/fgij/fg.htm?mol=9ltq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ltq OCA], [https://pdbe.org/9ltq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ltq RCSB], [https://www.ebi.ac.uk/pdbsum/9ltq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ltq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RAB43_HUMAN RAB43_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 set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. The low intrinsic GTPase activity of RAB43 is activated by USP6NL. 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 the structural integrity of the Golgi complex. Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis.<ref>PMID:17562788</ref> <ref>PMID:17684057</ref> <ref>PMID:18664496</ref> <ref>PMID:21255211</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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9ltq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Wang J]]
[[Category: Yan WP]]