6raj: Difference between revisions

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-'''Unreleased structure'''
-The entry 6raj is ON HOLD
+==Heterodimeric ABC exporter TmrAB in vanadate trapped outward-facing open conformation==
+<StructureSection load='6raj' size='340' side='right'caption='[[6raj]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6raj]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RAJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RAJ FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AOV:ADP+ORTHOVANADATE'>AOV</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6raj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6raj OCA], [http://pdbe.org/6raj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6raj RCSB], [http://www.ebi.ac.uk/pdbsum/6raj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6raj ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Cryo-electron microscopy (cryo-EM) has the capacity to capture molecular machines in action(1-3). ATP-binding cassette (ABC) exporters are highly dynamic membrane proteins that extrude a wide range of substances from the cytosol(4-6) and thereby contribute to essential cellular processes, adaptive immunity and multidrug resistance(7,8). Despite their importance, the coupling of nucleotide binding, hydrolysis and release to the conformational dynamics of these proteins remains poorly resolved, especially for heterodimeric and/or asymmetric ABC exporters that are abundant in humans. Here we present eight high-resolution cryo-EM structures that delineate the full functional cycle of an asymmetric ABC exporter in a lipid environment. Cryo-EM analysis under active turnover conditions reveals distinct inward-facing (IF) conformations-one of them with a bound peptide substrate-and previously undescribed asymmetric post-hydrolysis states with dimerized nucleotide-binding domains and a closed extracellular gate. By decreasing the rate of ATP hydrolysis, we could capture an outward-facing (OF) open conformation-an otherwise transient state vulnerable to substrate re-entry. The ATP-bound pre-hydrolysis and vanadate-trapped states are conformationally equivalent; both comprise co-existing OF conformations with open and closed extracellular gates. By contrast, the post-hydrolysis states from the turnover experiment exhibit asymmetric ATP and ADP occlusion after phosphate release from the canonical site and display a progressive separation of the nucleotide-binding domains and unlocking of the intracellular gate. Our findings reveal that phosphate release, not ATP hydrolysis, triggers the return of the exporter to the IF conformation. By mapping the conformational landscape during active turnover, aided by mutational and chemical modulation of kinetic rates to trap the key intermediates, we resolved fundamental steps of the substrate translocation cycle of asymmetric ABC transporters.
-Authors:
+Conformation space of a heterodimeric ABC exporter under turnover conditions.,Hofmann S, Januliene D, Mehdipour AR, Thomas C, Stefan E, Bruchert S, Kuhn BT, Geertsma ER, Hummer G, Tampe R, Moeller A Nature. 2019 Jul;571(7766):580-583. doi: 10.1038/s41586-019-1391-0. Epub 2019 Jul, 17. PMID:31316210<ref>PMID:31316210</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6raj" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Hofmann, S]]
+[[Category: Hummer, G]]
+[[Category: Januliene, D]]
+[[Category: Mehdipour, A R]]
+[[Category: Moeller, A]]
+[[Category: Tampe, R]]
+[[Category: Thomas, C]]
+[[Category: Atp-binding cassette transporter]]
+[[Category: Exporter]]
+[[Category: Heterodimer]]
+[[Category: Membrane protein]]
+[[Category: Transport protein]]