期刊
JOURNAL OF GENERAL PHYSIOLOGY
卷 134, 期 1, 页码 53-68出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1085/jgp.200910235
关键词
-
类别
资金
- National Institutes of Health [RO1GM62342, RO1HL61657]
K-2P phi, the two-pore domain potassium background channel that determines cardiac rhythm in Drosophila melanogaster, and its homologues that establish excitable membrane activity in mammals are of unknown structure. K-2P subunits have two pore domains flanked by transmembrane (TM) spans: TM1-P1-TM2-TM3-P2-TM4. To establish spatial relationships in K-2P phi, we identified pairs of sites that display electrostatic compensation. Channels silenced by the addition of a charge in pore loop 1 (P1) or P2 were restored to function by countercharges at specific second sites. A three-dimensional homology model was determined using the crystal structure of K(V)1.2, effects of K-2P phi mutations to establish alignment, and compensatory charge-charge pairs. The model was refined and validated by continuum electrostatic free energy calculations and covalent linkage of introduced cysteines. K2P channels use two subunits arranged so that the P1 and P2 loops contribute to one pore, identical P loops face each other diagonally across the pore, and the channel complex has bilateral symmetry with a fourfold symmetric selectivity filter.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据