STRUCTURE DETERMINATION OF KEF CHANNEL CYTOPLASMIC DOMAIN COMPLEX

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 KTN/RCK结构域调节多种K+转运系统和离子通道的跨膜通量。 许多争议围绕着调节机制，替代模型提出，一个组成的，构象灵活的八聚体环域，或四聚体和二聚体状态之间的化学计量重排，调节离子通量。 我们正在确定KTN结构域的结构，从Kef K+通道系统，在复杂的KefF辅助亚基，以解决这个问题。 另外令人感兴趣的是，KefF结合FMN，而KefC KTN结构域结合NAD（H），并且它们一起形成能够催化新型氧化还原化学的酶活性复合物。 因此，这项研究也将提高我们对跨膜离子电导和细胞生物化学如何联系起来创造更高阶现象（如记忆）的理解。

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. KTN/RCK domains regulate the transmembrane flux of a variety of K+ transport systems and ion channels. Much controversy surrounds the mechanism of regulation, with alternative models proposing either, a constitutive, conformationally-flexible octameric ring of domains, or stoichiometric rearrangements between tetrameric and dimeric states, modulating ion flux. We are determining the structure of the KTN domain from the Kef K+ channel system, in complex with its KefF ancillary subunit to resolve this issue. Of additional interest, KefF binds FMN while the KefC KTN domain binds NAD(H), and together they form an enzymatically active complex capable of catalyzing novel redox chemistry. Thus, this study will also improve our understanding of how transmembrane ion conductance and cellular biochemistry can be linked to create higher order phenomena such as memory.