TY - JOUR
T1 - Molecular basis of alternating access membrane transport by the sodium-hydantoin transporter Mhp1
AU - Shimamura, Tatsuro
AU - Weyand, Simone
AU - Beckstein, Oliver
AU - Rutherford, Nicholas G.
AU - Hadden, Jonathan M.
AU - Sharpies, David
AU - Sansom, Mark S.P.
AU - Iwata, So
AU - Henderson, Peter J.F.
AU - Cameron, Alexander D.
PY - 2010/4/23
Y1 - 2010/4/23
N2 - The structure of the sodium-benzylhydantoin transport protein Mhp1 from Microbacterium liquefaciens comprises a five-helix inverted repeat, which is widespread among secondary transporters. Here, we report the crystal structure of an inward-facing conformation of Mhp1 at 3.8 angstroms resolution, complementing its previously described structures in outward-facing and occluded states. From analyses of the three structures and molecular dynamics simulations, we propose a mechanism for the transport cycle in Mhp1. Switching from the outward- to the inward-facing state, to effect the inward release of sodium and benzylhydantoin, is primarily achieved by a rigid body movement of transmembrane helices 3, 4, 8, and 9 relative to the rest of the protein. This forms the basis of an alternating access mechanism applicable to many transporters of this emerging superfamily.
AB - The structure of the sodium-benzylhydantoin transport protein Mhp1 from Microbacterium liquefaciens comprises a five-helix inverted repeat, which is widespread among secondary transporters. Here, we report the crystal structure of an inward-facing conformation of Mhp1 at 3.8 angstroms resolution, complementing its previously described structures in outward-facing and occluded states. From analyses of the three structures and molecular dynamics simulations, we propose a mechanism for the transport cycle in Mhp1. Switching from the outward- to the inward-facing state, to effect the inward release of sodium and benzylhydantoin, is primarily achieved by a rigid body movement of transmembrane helices 3, 4, 8, and 9 relative to the rest of the protein. This forms the basis of an alternating access mechanism applicable to many transporters of this emerging superfamily.
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U2 - 10.1126/science.1186303
DO - 10.1126/science.1186303
M3 - Article
C2 - 20413494
AN - SCOPUS:77951585158
SN - 0036-8075
VL - 328
SP - 470
EP - 473
JO - Science
JF - Science
IS - 5977
ER -