View source for 6ral


==Heterodimeric ABC exporter TmrAB under turnover conditions in asymmetric unlocked return conformation==
<SX load='6ral' size='340' side='right' viewer='molstar' caption='[[6ral]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ral]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RAL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RAL FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</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'>[https://proteopedia.org/fgij/fg.htm?mol=6ral FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ral OCA], [https://pdbe.org/6ral PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ral RCSB], [https://www.ebi.ac.uk/pdbsum/6ral PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ral ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q72J05_THET2 Q72J05_THET2] 
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== 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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6ral" style="background-color:#fffaf0;"></div>

==See Also==
*[[ABC transporter 3D structures|ABC transporter 3D structures]]
== References ==
<references/>
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</SX>
[[Category: Large Structures]]
[[Category: Thermus thermophilus]]
[[Category: Vicugna pacos]]
[[Category: Hofmann S]]
[[Category: Hummer G]]
[[Category: Januliene D]]
[[Category: Mehdipour AR]]
[[Category: Moeller A]]
[[Category: Tampe R]]
[[Category: Thomas C]]