8fmv

Heterodimeric ABC transporter BmrCD in the inward-facing conformation bound to substrate and ATP: BmrCD_IF-2HT/ATP

spinqualitylabelsall models 8fmv, resolution 3.34Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8fmv is a 2 chain structure with sequence from Bacillus subtilis subsp. subtilis str. 168. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.34Å Ligands: ATP, HT1, MG, POV Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function YHEH_BACSU Involved in the transport of four structurally unrelated drugs, including doxorubicin and mitoxantrone. Transmembrane domains (TMD) form a pore in the membrane and the ATP-binding domain (NBD) is responsible for energy generation. Publication Abstract from PubMed Here we used cryo-electron microscopy (cryo-EM), double electron-electron resonance spectroscopy (DEER), and molecular dynamics (MD) simulations, to capture and characterize ATP- and substrate-bound inward-facing (IF) and occluded (OC) conformational states of the heterodimeric ATP binding cassette (ABC) multidrug exporter BmrCD in lipid nanodiscs. Supported by DEER analysis, the structures reveal that ATP-powered isomerization entails changes in the relative symmetry of the BmrC and BmrD subunits that propagates from the transmembrane domain to the nucleotide binding domain. The structures uncover asymmetric substrate and Mg(2+) binding which we hypothesize are required for triggering ATP hydrolysis preferentially in one of the nucleotide-binding sites. MD simulations demonstrate that multiple lipid molecules differentially bind the IF versus the OC conformation thus establishing that lipid interactions modulate BmrCD energy landscape. Our findings are framed in a model that highlights the role of asymmetric conformations in the ATP-coupled transport with general implications to the mechanism of ABC transporters. Asymmetric conformations and lipid interactions shape the ATP-coupled cycle of a heterodimeric ABC transporter.,Tang Q, Sinclair M, Hasdemir HS, Stein RA, Karakas E, Tajkhorshid E, Mchaourab HS Nat Commun. 2023 Nov 8;14(1):7184. doi: 10.1038/s41467-023-42937-5. PMID:37938578 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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