8dmo: Difference between revisions
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==Structure of open, inward-facing MsbA from E. coli== | |||
<StructureSection load='8dmo' size='340' side='right'caption='[[8dmo]], [[Resolution|resolution]] 3.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8dmo]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DMO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DMO FirstGlance]. <br> | |||
</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=8dmo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dmo OCA], [https://pdbe.org/8dmo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dmo RCSB], [https://www.ebi.ac.uk/pdbsum/8dmo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dmo ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/C3TGA2_ECOLX C3TGA2_ECOLX] Involved in lipid A export and possibly also in glycerophospholipid export and for biogenesis of the outer membrane. Transmembrane domains (TMD) form a pore in the inner membrane and the ATP-binding domain (NBD) is responsible for energy generation.[HAMAP-Rule:MF_01703][SAAS:SAAS00055332] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A critical step in lipopolysaccharide (LPS) biogenesis involves flipping lipooligosaccharide, an LPS precursor, from the cytoplasmic to the periplasmic leaflet of the inner membrane, an operation carried out by the ATP-binding cassette transporter MsbA. Although LPS binding to the inner cavity of MsbA is well established, the selectivity of MsbA-lipid interactions at other site(s) remains poorly understood. Here we use native mass spectrometry (MS) to characterize MsbA-lipid interactions and guide structural studies. We show the transporter co-purifies with copper(II) and metal binding modulates protein-lipid interactions. A 2.15 A resolution structure of an N-terminal region of MsbA in complex with copper(II) is presented, revealing a structure reminiscent of the GHK peptide, a high-affinity copper(II) chelator. Our results demonstrate conformation-dependent lipid binding affinities, particularly for the LPS-precursor, 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo)(2)-lipid A (KDL). We report a 3.6 A-resolution structure of MsbA trapped in an open, outward-facing conformation with adenosine 5'-diphosphate and vanadate, revealing a distinct KDL binding site, wherein the lipid forms extensive interactions with the transporter. Additional studies provide evidence that the exterior KDL binding site is conserved and a positive allosteric modulator of ATPase activity, serving as a feedforward activation mechanism to couple transporter activity with LPS biosynthesis. | |||
Structural basis for lipid and copper regulation of the ABC transporter MsbA.,Lyu J, Liu C, Zhang T, Schrecke S, Elam NP, Packianathan C, Hochberg GKA, Russell D, Zhao M, Laganowsky A Nat Commun. 2022 Nov 26;13(1):7291. doi: 10.1038/s41467-022-34905-2. PMID:36435815<ref>PMID:36435815</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8dmo" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli]] | |||
[[Category: Large Structures]] | |||
[[Category: Laganowsky AD]] | |||
[[Category: Liu C]] | |||
[[Category: Lyu J]] | |||
[[Category: Zhao M]] | |||
