PT  - JOURNAL ARTICLE
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
TI  - Structure-based analysis of CysZ-mediated cellular uptake of sulfate
AID  - 10.1101/131318
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 131318
4099  - http://biorxiv.org/content/early/2017/04/27/131318.short
4100  - http://biorxiv.org/content/early/2017/04/27/131318.full
AB  - 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.