Crystallographic studies of the conformational changes that drive directional transmembrane ion movement in bacteriorhodopsin.
Recent advances in the determination of the X-ray crystallographic structures of bacteriorhodopsin, and some of its photointermediates, reveal the nature of the linkage between the relaxation of electrostatic and steric conflicts at the retinal and events elsewhere in the protein. The transport cycle can be now understood in terms of specific and well-described displacements of hydrogen-bonded water, and main-chain and side-chain atoms, that lower the pK(a)s of the proton release group in the extracellular region and Asp-96 in the cytoplasmic region. Thus, local electrostatic conflict of the photoisomerized retinal with Asp-85 and Asp-212 causes deprotonation of the Schiff base, and results in a cascade of events culminating in proton release to the extracellular surface. Local steric conflict of the 13-methyl group with Trp-182 causes, in turn, a cascade of movements in the cytoplasmic region, and results in reprotonation of the Schiff base. Although numerous questions concerning the mechanism of each of these proton (or perhaps hydroxyl ion) transfers remain, the structural results provide a detailed molecular explanation for how the directionality of the ion transfers is determined by the configurational relaxation of the retinal.
Lanyi
J K
JK
Department of Physiology and Biophysics, University of California, Irvine 92697, USA. jlanyi@orion.oac.uci.edu
D001436:Bacteriorhodopsins / Q000737:chemistry* / Q000378:metabolism; D003461:Crystallography; D004735:Energy Transfer; D017136:Ion Transport; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D011487:Protein Conformation; D021381:Protein Transport; D012172:Retinaldehyde / Q000737:chemistry; D014961:X-Ray Diffraction
D008565:Membrane Proteins; D001436:Bacteriorhodopsins; D012172:Retinaldehyde