View source for 8chb


==Inward-facing conformation of the ABC transporter BmrA C436S/A582C cross-linked mutant==
<StructureSection load='8chb' size='340' side='right'caption='[[8chb]], [[Resolution|resolution]] 3.14&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8chb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8CHB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CHB 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]] 3.14&#8491;</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=8chb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8chb OCA], [https://pdbe.org/8chb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8chb RCSB], [https://www.ebi.ac.uk/pdbsum/8chb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8chb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BMRA_BACSU BMRA_BACSU] An efflux transporter able to transport Hoechst 33342, ethidium bromide, doxorubicin and a number of other drugs in vitro into inside out vesicles. The endogenous substrate is unknown. It has been suggested that NBD dimerization induced by ATP-binding causes a large conformational change responsible for substrate translocation (PubMed:18215075). Transmembrane domains (TMD) form a pore in the inner membrane and the ATP-binding domain (NBD) is responsible for energy generation (Probable).<ref>PMID:18215075</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
ATP-binding cassette (ABC) transporters are ubiquitous membrane proteins responsible for the translocation of a wide diversity of substrates across biological membranes. Some of them confer multidrug or antimicrobial resistance to cancer cells and pathogenic microorganisms, respectively. Despite a wealth of structural data gained in the last two decades, the molecular mechanism of these multidrug efflux pumps remains elusive, including the extent of separation between the two nucleotide-binding domains (NBDs) during the transport cycle. Based on recent outward-facing structures of BmrA, a homodimeric multidrug ABC transporter from Bacillus subtilis, we introduced a cysteine mutation near the C-terminal end of the NBDs to analyze the impact of disulfide-bond formation on BmrA function. Interestingly, the presence of the disulfide bond between the NBDs did not prevent the ATPase, nor did it affect the transport of Hoechst 33342 and doxorubicin. Yet, the 7-amino-actinomycin D was less efficiently transported, suggesting that a further opening of the transporter might improve its ability to translocate this larger compound. We solved by cryo-EM the apo structures of the cross-linked mutant and the WT protein. Both structures are highly similar, showing an intermediate opening between their NBDs while their C-terminal extremities remain in close proximity. Distance measurements obtained by electron paramagnetic resonance spectroscopy support the intermediate opening found in these 3D structures. Overall, our data suggest that the NBDs of BmrA function with a tweezers-like mechanism distinct from the related lipid A exporter MsbA.

The transport activity of the multidrug ABC transporter BmrA does not require a wide separation of the nucleotide-binding domains.,Di Cesare M, Kaplan E, Rendon J, Gerbaud G, Valimehr S, Gobet A, Ngo TT, Chaptal V, Falson P, Martinho M, Dorlet P, Hanssen E, Jault JM, Orelle C J Biol Chem. 2024 Jan;300(1):105546. doi: 10.1016/j.jbc.2023.105546. Epub 2023 , Dec 9. PMID:38072053<ref>PMID:38072053</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8chb" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacillus subtilis]]
[[Category: Large Structures]]
[[Category: Di Cesare M]]
[[Category: Hanssen E]]
[[Category: Jault JM]]
[[Category: Kaplan E]]
[[Category: Orelle C]]
[[Category: Valimehr S]]