8dmm

Structure of the vanadate-trapped MsbA bound to KDL

spinqualitylabelsall models 8dmm, resolution 3.47Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8dmm is a 2 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.47Å Ligands: AOV, KDL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MSBA_ECOLI 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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