MEMBRANE PROTEINS INVOLVED IN ION TRANSPORT

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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Gating is the major mode of regulation of potassium channels; stimuli alter the equilibrium between the open and closed states of the ion pore letting ions flow through the channel. The structures of the KcsA channel (closed state) and the MthK channel (open state) revealed the molecular characteristics of the two gating states but we still do not understand clearly how stimuli induce the conformational change. We are working on the structure determination of a potassium channel that is gated by cAMP. We have recently determined the structure of its regulatory domain in both the bound and unbound conformations; this structure has provide interesting and important insights to the conformational changes that occur at the level of the cyclic-nucleotide binding domain upon ligand binding and has led us to proposed a model for channel gating. We are now expressing and growing crystals of the full-length channel. This tetrameric membrane protein has 6 putative transmembrane segments (TMs) per subunit; the last 2 TMs form the ion conduction pathway first revealed by the structure of the KcsA potassium channel; at the C-terminus there is a ~150 residue cytoplasmic cyclic-nucleotide binding domain.