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Title: Structure-based analysis of CysZ-mediated cellular uptake of sulfate

Abstract

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. However, current understanding of the cellular delivery of SO42- at the molecular level is limited. 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 flux experiments, we provide insight into the molecular mechanism of CysZ-mediated translocation of SO42- across membranes. CysZ structures from three different bacterial species display a hitherto unknown fold and have subunits organized with inverted transmembrane topology. CysZ from Pseudomonas denitrificans assembles as a trimer of antiparallel dimers and the CysZ structures from two other species recapitulate dimers from this assembly. Mutational studies highlight the functional relevance of conserved CysZ residues.

Authors:
 [1];  [2]; ORCiD logo [3];  [4];  [5];  [1];  [6];  [7];  [7];  [7];  [8];  [9];  [9];  [10];  [6];  [11];  [12]; ORCiD logo [4]
  1. Department of Physiology and Cellular Biophysics, Columbia University, New York, United States; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, United States
  2. Biology Department, Brookhaven National Laboratory, Upton, United States
  3. Department of Biochemistry and Molecular Biophysics, Columbia University, New York, United States
  4. Department of Physiology and Cellular Biophysics, Columbia University, New York, United States
  5. Center for Molecular Recognition, Department of Psychiatry, Columbia University, New York, United States
  6. Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, United States; Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, United States
  7. New York Structural Biology Center, New York, United States
  8. Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom
  9. Department of Chemistry and Chemical Biology, Cornell University, NE-CAT, Argonne, United States
  10. Department of Informatics, Technical University of Munich, Munich, Germany
  11. Center for Molecular Recognition, Department of Psychiatry, Columbia University, New York, United States; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, United States
  12. Department of Physiology and Cellular Biophysics, Columbia University, New York, United States; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, United States; New York Structural Biology Center, New York, United States
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
NIGMS
OSTI Identifier:
1440601
Resource Type:
Journal Article
Resource Relation:
Journal Name: eLife; Journal Volume: 7; Journal Issue: 2018
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Assur Sanghai, Zahra, Liu, Qun, Clarke, Oliver B., Belcher-Dufrisne, Meagan, Wiriyasermkul, Pattama, Giese, M. Hunter, Leal-Pinto, Edgar, Kloss, Brian, Tabuso, Shantelle, Love, James, Punta, Marco, Banerjee, Surajit, Rajashankar, Kanagalaghatta R., Rost, Burkhard, Logothetis, Diomedes, Quick, Matthias, Hendrickson, Wayne A., and Mancia, Filippo. Structure-based analysis of CysZ-mediated cellular uptake of sulfate. United States: N. p., 2018. Web. doi:10.7554/eLife.27829.
Assur Sanghai, Zahra, Liu, Qun, Clarke, Oliver B., Belcher-Dufrisne, Meagan, Wiriyasermkul, Pattama, Giese, M. Hunter, Leal-Pinto, Edgar, Kloss, Brian, Tabuso, Shantelle, Love, James, Punta, Marco, Banerjee, Surajit, Rajashankar, Kanagalaghatta R., Rost, Burkhard, Logothetis, Diomedes, Quick, Matthias, Hendrickson, Wayne A., & Mancia, Filippo. Structure-based analysis of CysZ-mediated cellular uptake of sulfate. United States. doi:10.7554/eLife.27829.
Assur Sanghai, Zahra, Liu, Qun, Clarke, Oliver B., Belcher-Dufrisne, Meagan, Wiriyasermkul, Pattama, Giese, M. Hunter, Leal-Pinto, Edgar, Kloss, Brian, Tabuso, Shantelle, Love, James, Punta, Marco, Banerjee, Surajit, Rajashankar, Kanagalaghatta R., Rost, Burkhard, Logothetis, Diomedes, Quick, Matthias, Hendrickson, Wayne A., and Mancia, Filippo. Thu . "Structure-based analysis of CysZ-mediated cellular uptake of sulfate". United States. doi:10.7554/eLife.27829.
@article{osti_1440601,
title = {Structure-based analysis of CysZ-mediated cellular uptake of sulfate},
author = {Assur Sanghai, Zahra and Liu, Qun and Clarke, Oliver B. and Belcher-Dufrisne, Meagan and Wiriyasermkul, Pattama and Giese, M. Hunter and Leal-Pinto, Edgar and Kloss, Brian and Tabuso, Shantelle and Love, James and Punta, Marco and Banerjee, Surajit and Rajashankar, Kanagalaghatta R. and Rost, Burkhard and Logothetis, Diomedes and Quick, Matthias and Hendrickson, Wayne A. and Mancia, Filippo},
abstractNote = {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. However, current understanding of the cellular delivery of SO42- at the molecular level is limited. 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 flux experiments, we provide insight into the molecular mechanism of CysZ-mediated translocation of SO42- across membranes. CysZ structures from three different bacterial species display a hitherto unknown fold and have subunits organized with inverted transmembrane topology. CysZ from Pseudomonas denitrificans assembles as a trimer of antiparallel dimers and the CysZ structures from two other species recapitulate dimers from this assembly. Mutational studies highlight the functional relevance of conserved CysZ residues.},
doi = {10.7554/eLife.27829},
journal = {eLife},
number = 2018,
volume = 7,
place = {United States},
year = {Thu May 24 00:00:00 EDT 2018},
month = {Thu May 24 00:00:00 EDT 2018}
}