First structure of a eukaryotic phosphate transporter revealed
Robert Stroud group (University of California - San Francisco) and collaborators
Phosphate is crucial for structural and metabolic needs
including nucleotide and lipid synthesis, signaling, and chemical energy
storage. Phosphate-uptake is mediated by proton-coupled transporters of the
Major Facilitator Super-family in plants and fungi. A collaborative research
group headed by Robert Stroud succeeded in obtaining the first
high-resolution structure of a phosphate transporter using GM/CA@APS
beamlines. The 2.9-Å structure of the fungal high-affinity phosphate
importer was solved in an inward-facing occluded state with bound phosphate
visible in the membrane-buried binding site. The structure indicated both
proton and phosphate exit pathways and suggested a modified asymmetrical
'Rocker-Switch' mechanism of phosphate transport, deviating from the
canonical major facilitator transport model. The phosphate transporter 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. The structure demonstrates and expands
on principles of substrate transport by the Major Facilitator Super-family
and illuminates principles of phosphate uptake in particular.
Figure: The high affinity phosphate
transporter in ribbon representation. The two domains of the transporter are
colored in blue and green and the centrally located phosphate is colored
orange. The black bars denote the approximate location of the membrane.
Citation: Pedersen BP, Kumar H, Waight AB, Risenmay AJ,
Roe-Zurz Z, Chau BH, Schlessinger A, Bonomi M, Harries W, Sali A, Johri AK,
Stroud RM. Crystal structure of a eukaryotic phosphate transporter. Nature.
2013 Apr 25;496:533-536.