Structural evidence for induced fit and a mechanism for sugar/H+ symport in LacY.
Cation-coupled active transport is an essential cellular process found ubiquitously in all living organisms. Here, we present two novel ligand-free X-ray structures of the lactose permease (LacY) of Escherichia coli determined at acidic and neutral pH, and propose a model for the mechanism of coupling between lactose and H+ translocation. No sugar-binding site is observed in the absence of ligand, and deprotonation of the key residue Glu269 is associated with ligand binding. Thus, substrate induces formation of the sugar-binding site, as well as the initial step in H+ transduction.
Mirza
Osman
O
Department of Biological Sciences, Membrane Protein Crystallography Group, Imperial College London, London, UK.
Guan
Lan
L
Verner
Gill
G
Iwata
So
S
Kaback
H Ronald
HR
D001665:Binding Sites; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport; D007785:Lactose / Q000378:metabolism*; D008024:Ligands; D009004:Monosaccharide Transport Proteins / Q000737:chemistry*; D011487:Protein Conformation; D013379:Substrate Specificity; D027981:Symporters / Q000737:chemistry*; D014961:X-Ray Diffraction
D029968:Escherichia coli Proteins; C050221:LacY protein, E coli; D008024:Ligands; D009004:Monosaccharide Transport Proteins; D027981:Symporters; D007785:Lactose