PubMed 26063437
Referenced in: none
Automatically associated channels: Kir2.1
Title: Identification of the Conformational transition pathway in PIP2 Opening Kir Channels.
Authors: Junwei Li, Shouqin Lü, Yuzhi Liu, Chunli Pang, Yafei Chen, Suhua Zhang, Hui Yu, Mian Long, Hailin Zhang, Diomedes E Logothetis, Yong Zhan, Hailong An
Journal, date & volume: Sci Rep, 2015 , 5, 11289
PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26063437
Abstract
The gating of Kir channels depends critically on phosphatidylinositol 4,5-bisphosphate (PIP2), but the detailed mechanism by which PIP2 regulates Kir channels remains obscure. Here, we performed a series of Targeted molecular dynamics simulations on the full-length Kir2.1 channel and, for the first time, were able to achieve the transition from the closed to the open state. Our data show that with the upward motion of the cytoplasmic domain (CTD) the structure of the C-Linker changes from a loop to a helix. The twisting of the C-linker triggers the rotation of the CTD, which induces a small downward movement of the CTD and an upward motion of the slide helix toward the membrane that pulls the inner helix gate open. At the same time, the rotation of the CTD breaks the interaction between the CD- and G-loops thus releasing the G-loop. The G-loop then bounces away from the CD-loop, which leads to the opening of the G-loop gate and the full opening of the pore. We identified a series of interaction networks, between the N-terminus, CD loop, C linker and G loop one by one, which exquisitely regulates the global conformational changes during the opening of Kir channels by PIP2.