Publication

Article Metrics

Citations


Online attention

Structure and molecular mechanism of a nucleobase-cation symport-1 family transporter

DOI: 10.1126/science.1164440 DOI Help
PMID: 18927357 PMID Help

Authors: Simone Weyand (Membrane Protein Laboratory, Diamond Light Source Limited) , Tatsuro Shimamura (Imperial College, London) , Shunsuke Yajima (Imperial College, London) , Shunichi Suzuki (University of Leeds) , Osman Mirza (Imperial College, London) , Kuakarun Krusong (Imperial College, London) , Liz Carpenter (Diamond Light Source) , Nicholas G. Rutherford (University of Leeds) , Jonathan M. Hadden (University of Leeds) , John O'reilly (University of Leeds) , Pikyee Ma (University of Leeds) , Massoud Saidjam (University of Leeds; Hamedan University of Medical Sciences) , Simon G. Patching (University of Leeds) , Ryan J. Hope (University of Leeds) , Halina T. Norbertczak (University of Leeds) , Peter C. J. Roach (University of Leeds) , So Iwata (Diamond Light Source; Imperial College, London; Human Receptor Crystallography Project, Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Agency; Kyoto University; RIKEN) , Peter J. F. Henderson (University of Leeds) , Alexander D. Cameron (Diamond Light Source; Imperial College, London; Human Receptor Crystallography Project, Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Agency)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science , VOL 322 (5902) , PAGES 709 - 713

State: Published (Approved)
Published: October 2008
Diamond Proposal Number(s): 456

Abstract: The nucleobase–cation–symport-1 (NCS1) transporters are essential components of salvage pathways for nucleobases and related metabolites. Here, we report the 2.85-angstrom resolution structure of the NCS1 benzyl-hydantoin transporter, Mhp1, from Microbacterium liquefaciens. Mhp1 contains 12 transmembrane helices, 10 of which are arranged in two inverted repeats of five helices. The structures of the outward-facing open and substrate-bound occluded conformations were solved, showing how the outward-facing cavity closes upon binding of substrate. Comparisons with the leucine transporter LeuTAa and the galactose transporter vSGLT reveal that the outward- and inward-facing cavities are symmetrically arranged on opposite sides of the membrane. The reciprocal opening and closing of these cavities is synchronized by the inverted repeat helices 3 and 8, providing the structural basis of the alternating access model for membrane transport.

Journal Keywords: Transporter molecular mechanism

Subject Areas: Physics

Diamond Offline Facilities: Membrane Protein Laboratory (MPL)

Facility: ESRF/SLS