Molecular basis of alternating access membrane transport by the sodium-hydantoin transporter Mhp1.
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.
Shimamura
Tatsuro
T
Division of Molecular Biosciences, Membrane Protein Crystallography Group, Imperial College, London SW7 2AZ, UK.
Weyand
Simone
S
Beckstein
Oliver
O
Rutherford
Nicholas G
NG
Hadden
Jonathan M
JM
Sharples
David
D
Sansom
Mark S P
MS
Iwata
So
S
Henderson
Peter J F
PJ
Cameron
Alexander D
AD
D000192:Actinomycetales / Q000737:chemistry* / Q000378:metabolism; D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D001692:Biological Transport; D018360:Crystallography, X-Ray; D006827:Hydantoins / Q000737:chemistry / Q000378:metabolism*; D017136:Ion Transport; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012964:Sodium / Q000378:metabolism*
D001426:Bacterial Proteins; D006827:Hydantoins; D026901:Membrane Transport Proteins; D012964:Sodium