MEMBRANE PROTEINS INVOLVED IN ION TRANSPORT

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。门控是钾离子通道调控的主要方式；刺激改变离子孔的开放和关闭状态之间的平衡，使离子通过通道。KcsA通道（封闭状态）和MthK通道（开放状态）的结构揭示了两种门控状态的分子特征，但我们仍然不清楚刺激是如何引起构象变化的。我们正在研究cAMP门控的钾离子通道的结构。我们最近确定了其结合构象和非结合构象的调控结构域的结构；这种结构为配体结合时在环核苷酸结合域水平上发生的构象变化提供了有趣而重要的见解，并使我们提出了通道门控模型。我们现在正在表达和生长全长通道的晶体。这种四聚体膜蛋白每个亚基有6个假定的跨膜片段（TMs）；后2个TMs形成由KcsA钾通道结构首先揭示的离子传导途径；在c端有约150个残基胞质环核苷酸结合域。

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.