6par | pdb_00006par

Structure of a bacterial Atm1-family ABC exporter with MgAMPPNP bound

spinqualitylabelsall models 6par, resolution 3.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6par is a 6 chain structure with sequence from Novosphingobium aromaticivorans DSM 12444. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.35Å Ligands: ANP, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ATM1_NOVAD Mediates the ATP-dependent export of glutathione-conjugated substrates, such as heavy metal-glutathione conjugates. ATP hydrolysis is stimulated by glutathione binding. Protects cells against toxic heavy metal ions, such as silver and mercury ions. May also mediate the transport of glutathione-conjugated aromatic hydrocarbons, such as dinitrobenzene. Publication Abstract from PubMed The ATP-binding cassette (ABC) transporter of mitochondria (Atm1) mediates iron homeostasis in eukaryotes, while the prokaryotic homolog from Novosphingobium aromaticivorans (NaAtm1) can export glutathione derivatives and confer protection against heavy-metal toxicity. To establish the structural framework underlying the NaAtm1 transport mechanism, we determined eight structures by X-ray crystallography and single-particle cryo-electron microscopy in distinct conformational states, stabilized by individual disulfide crosslinks and nucleotides. As NaAtm1 progresses through the transport cycle, conformational changes in transmembrane helix 6 (TM6) alter the glutathione-binding site and the associated substrate-binding cavity. Significantly, kinking of TM6 in the post-ATP hydrolysis state stabilized by MgADPVO4 eliminates this cavity, precluding uptake of glutathione derivatives. The presence of this cavity during the transition from the inward-facing to outward-facing conformational states, and its absence in the reverse direction, thereby provide an elegant and conceptually simple mechanism for enforcing the export directionality of transport by NaAtm1. One of the disulfide crosslinked NaAtm1 variants characterized in this work retains significant glutathione transport activity, suggesting that ATP hydrolysis and substrate transport by Atm1 may involve a limited set of conformational states with minimal separation of the nucleotide-binding domains in the inward-facing conformation. A structural framework for unidirectional transport by a bacterial ABC exporter.,Fan C, Kaiser JT, Rees DC Proc Natl Acad Sci U S A. 2020 Aug 11;117(32):19228-19236. doi:, 10.1073/pnas.2006526117. Epub 2020 Jul 23. PMID:32703810 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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