TY - JOUR T1 - Structure-based analysis of CysZ-mediated cellular uptake of sulfate JF - bioRxiv DO - 10.1101/131318 SP - 131318 AU - Zahra Assur Sanghai AU - Qun Liu AU - Oliver B. Clarke AU - Edgar Leal Pinto AU - Brian Kloss AU - Shantelle Tabuso AU - James Love AU - Marco Punta AU - Surajit Banerjee AU - Kanagalaghatta R. Rajashankar AU - Burkhard Rost AU - Diomedes Logothetis AU - Matthias Quick AU - Wayne A. Hendrickson AU - Filippo Mancia Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/04/26/131318.abstract N2 - Sulfur, most abundantly found in the environment as sulfate (SO42-), is an essential element in metabolites required by all living cells, including amino acids, co-factors and vitamins. Current understanding of the cellular delivery of SO42- at the molecular level is limited however. CysZ has been described as a SO42- permease, but its sequence family is without known structural precedent. Based on crystallographic structure information, SO42- binding and uptake experiments in cells and proteoliposomes, and single-channel conductance measurements, we provide insight into the molecular mechanism of CysZ-mediated translocation of SO42- across membranes. CysZ properties differ markedly from those of known transporters and ion channels. The structures display a hitherto unknown fold with dual topology, assembling in CysZ from Pseudomonas denitrificans as a trimer of antiparallel dimers in the membrane. CysZ structures from two other species recapitulate dimers from this assembly. Mutational studies highlight the functional relevance of conserved CysZ residues. ER -