GLUTAMATE TRANSPORTER HOMOLOGUE FROM PYROCCOCUS HORIKOSHII

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Glutamate transporters are integral membrane proteins responsible for clearance of glutamate from the synaptic cleft following rounds of neurotransmission. Glutamate transporters couple substrate uptake to membrane gradients of sodium, potassium and protons. In addition to thermodynamically coupled ion fluxes they also demonstrate an uncoupled anion flux, which is gated by substrate binding. Recently we have determined the crystal structure of a glutamate transporter homologue from Pyroccocus horikoshii (GltPh) (Nature 431: 811-18, 2004; Nature 445: 387-93, 2007). It has been consequently demonstrated that this protein captures many functional features of its mammalian homologues, including anion permeation. We are planning to use anions containing heavy atoms to attempt to locate anion permeation pathway/binding sites. This work will shed light on the mechanism of these intriguing and physiologically hugely important proteins, that combine features of ion coupled transporters and ion channels.