STRUCTURAL BASIS FOR K+ CHANNEL SLOW INACTIVATION

K 通道缓慢失活的结构基础

• 批准号: 8169261
• 负责人: Eduardo A Perozo
• 金额: $ 2.44万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169261
• 关键词: Complex; Computer Retrieval of Information on Scientific Projects Database; Funding; Grant; Institution; Molecular Analysis; Molecular Conformation; Mutation; Research; Research Personnel; Resources; Source; Structure; United States National Institutes of Health; base; design; mutant; prokaryotic potassium channel; sensor; Complex; Computer Retrieval of Information on Scientific Projects Database; Funding; Grant; Institution; Molecular Analysis; Molecular Conformation; Mutation; Research; Research Personnel; Resources; Source; Structure; United States National Institutes of Health; base; design; mutant; prokaryotic potassium channel; sensor

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. Analysis of the molecular identity of the pH sensor in the prokaryotic potassium channel KcsA identified several key mutants that stabilized the KcsA inner bundle gate in the fully open conformation at neutral pH, a fact that makes possible the crystallographic analyses of KcsA in a variety of functional states. As a first approach, we planned to determine the crystal structure of open KcsA via analysis of several of these constitutively open KcsA mutants. Additional mutations in the selectivity filter were designed towards the determination of a fully conductive and an inactivated form of the channel. A preliminary crystal structure of one of these mutants in complex with a Fab has provided tantalizing new information regarding the mechanism of gate opening in KcsA and a likely path towards the fully open state.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 对原核钾通道KCSA中pH传感器的分子身份的分析确定了几个关键突变体，这些突变体稳定了中性pH的完全开放构型中的KCSA内束门，这一事实使KCSA在多种功能状态中的晶体学分析成为可能。作为第一种方法，我们计划通过分析其中几个组成型开放的KCSA突变体来确定开放式KCSA的晶体结构。 选择性滤波器中的其他突变是为确定通道的完全导电形式和灭活形式而设计的。这些与Fab中的其中一个突变体之一的初步晶体结构提供了有关KCSA栅极开口机理的诱人新信息，并可能是通往完全开放状态的路径。