Crystal structure of a eukaryotic phosphate transporter

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Bjørn Panyella Pedersen
  • Hemant Kumar, Department of Biochemistry and Biophysics, University of California, San Francisco, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India, United States
  • Andrew B Waight, Department of Biochemistry and Biophysics, University of California, San Francisco, United States
  • Aaron J Risenmay, Department of Biochemistry and Biophysics, University of California, San Francisco, United States
  • Zygy Roe-Zurz, Department of Biochemistry and Biophysics, University of California, San Francisco, United States
  • Bryant H Chau, Department of Biochemistry and Biophysics, University of California, San Francisco, United States
  • Avner Schlessinger, Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, University of California, San Francisco, California 94158, USA, United States
  • Massimiliano Bonomi, Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, University of California, San Francisco, California 94158, USA, United States
  • William Harries, Department of Biochemistry and Biophysics, University of California, San Francisco, United States
  • Andrej Sali, Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, University of California, San Francisco, California 94158, USA, United States
  • Atul K Johri, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India, India
  • Robert M Stroud, Department of Biochemistry and Biophysics, University of California, San Francisco, United States

Phosphate is crucial for structural and metabolic needs, including nucleotide and lipid synthesis, signalling and chemical energy storage. Proton-coupled transporters of the major facilitator superfamily (MFS) are essential for phosphate uptake in plants and fungi, and also have a function in sensing external phosphate levels as transceptors. Here we report the 2.9 Å structure of a fungal (Piriformospora indica) high-affinity phosphate transporter, PiPT, in an inward-facing occluded state, with bound phosphate visible in the membrane-buried binding site. The structure indicates both proton and phosphate exit pathways and suggests a modified asymmetrical 'rocker-switch' mechanism of phosphate transport. PiPT is related to several human transporter families, most notably the organic cation and anion transporters of the solute carrier family (SLC22), which are implicated in cancer-drug resistance. We modelled representative cation and anion SLC22 transporters based on the PiPT structure to surmise the structural basis for substrate binding and charge selectivity in this important family. The PiPT structure demonstrates and expands on principles of substrate transport by the MFS transporters and illuminates principles of phosphate uptake in particular.

Original languageEnglish
JournalNature
Volume496
Issue7446
Pages (from-to)533-536
Number of pages4
ISSN0028-0836
DOIs
Publication statusPublished - 25 Apr 2013

    Research areas

  • Basidiomycota, Binding Sites, Crystallography, X-Ray, Eukaryotic Cells, Humans, Models, Biological, Models, Molecular, Phosphate Transport Proteins, Phosphates, Protein Conformation, Protons, Structure-Activity Relationship

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