Reassessing the helix bundle crossing model for gating in a non-selective ion channel

Author:

Kurauskas Vilius,Tonelli Marco,Henzler-Wildman Katherine

Abstract

ABSTRACTA critical part of ion channel function is the ability to open and close in response to stimuli, and thus conduct ions in a regulated fashion. While X-ray diffraction studies of ion channels suggested a general steric gating mechanism located at the helix bundle crossing (HBC), recent functional studies on several channels indicate that the helix bundle crossing is open even in closed, non-conductive channels. Two NaK channel variants were crystallized in very different, open and closed conformations and served as an important model of the HBC gating hypothesis. However, neither of these NaK variants are conductive in liposomes unless phenylalanine 92 is mutated to alanine (F92A). Here we use NMR to probe distances at near-atomic resolution of the two NaK variants in lipid bicelles. We demonstrate that in contrast to the crystal structures, both NaK variants are in a fully open conformation, akin to the well known MthK channel structure were the HBC is widely open. Further inquiry into the gating mechanism suggests that the selectivity filter and pore helix are coupled to the M2 helix below and undergo changes in structure when F92 is mutated. Overall, our data shows that NaK exhibits coupling between the selectivity filter and HBC similar to K+ channels and has a more complex gating mechanism than previously thought.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3