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

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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 对原核生物钾通道KCSA中pH传感器的分子同一性分析确定了几个关键突变体，它们在中性pH下稳定了KCSA内束门的全开放构象，这一事实使KCSA在各种功能状态下的结晶学分析成为可能。作为第一种方法，我们计划通过分析几个结构性开放的KCSA突变体来确定开放的KCSA的晶体结构。 选择性过滤器中的附加突变被设计用于确定通道的完全导电和失活形式。其中一个突变体与Fab形成的复合体的初步晶体结构为KCSA的门打开机制和通向完全开放状态的可能途径提供了诱人的新信息。