Conformational change in an MFS protein: MD simulations of LacY.
Molecular dynamics simulations of lactose permease (LacY) in a phospholipid bilayer reveal the conformational dynamics of the protein. In inhibitor-bound simulations (i.e., those closest to the X-ray structure) the protein was stable, showing little conformational change over a 50 ns timescale. Movement of the bound inhibitor, TDG, to an alternative binding mode was observed, so that it interacted predominantly with the N-terminal domain and with residue E269 from the C-terminal domain. In multiple ligand-free simulations, a degree of domain closure occurred. This switched LacY to a state with a central cavity closed at both the intracellular and periplasmic ends. This may resemble a possible intermediate in the transport mechanism. Domain closure occurs by a combination of rigid-body movements of domains and of intradomain motions of helices, especially TM4, TM5, TM10, and TM11. A degree of intrahelix flexibility appears to be important in the conformational change.
Holyoake
John
J
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.
Sansom
Mark S P
MS
D003198:Computer Simulation; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D026901:Membrane Transport Proteins / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013862:Thiogalactosides / Q000737:chemistry
D008051:Lipid Bilayers; D026901:Membrane Transport Proteins; D013862:Thiogalactosides; C031803:thiodigalactoside; C021499:lactose permease; D004134:Dimyristoylphosphatidylcholine