Molecular Dynamics Simulations of KirBac1.1 Mutants Reveal Global Gating Changes of Kir Channels

Journal of Chemical Information and Modeling
Tobias LinderAnna Stary-Weinzinger

Abstract

Prokaryotic inwardly rectifying (KirBac) potassium channels are homologous to mammalian Kir channels. Their activity is controlled by dynamical conformational changes that regulate ion flow through a central pore. Understanding the dynamical rearrangements of Kir channels during gating requires high-resolution structure information from channels crystallized in different conformations and insight into the transition steps, which are difficult to access experimentally. In this study, we use MD simulations on wild type KirBac1.1 and an activatory mutant to investigate activation gating of KirBac channels. Full atomistic MD simulations revealed that introducing glutamate in position 143 causes significant widening at the helix bundle crossing gate, enabling water flux into the cavity. Further, global rearrangements including a twisting motion as well as local rearrangements at the subunit interface in the cytoplasmic domain were observed. These structural rearrangements are similar to recently reported KirBac3.1 crystal structures in closed and open conformation, suggesting that our simulations capture major conformational changes during KirBac1.1 opening. In addition, an important role of protein-lipid interactions during gating ...Continue Reading

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Citations

Jan 23, 2017·Biochemical and Biophysical Research Communications·Harald BernsteinerAnna Stary-Weinzinger
Apr 9, 2017·The Journal of General Physiology·William F BorschelColin G Nichols
Sep 13, 2019·The Journal of General Physiology·Harald BernsteinerAnna Stary-Weinzinger
Jul 22, 2016·Scientific Reports·Xuan-Yu MengDiomedes E Logothetis
Jan 26, 2020·Proceedings of the National Academy of Sciences of the United States of America·Reza AmaniBenjamin J Wylie
Jun 29, 2018·Pflügers Archiv : European journal of physiology·S HeringE N Timin
Nov 21, 2019·The Journal of General Physiology·Eva-Maria Zangerl-PlesslColin G Nichols
Jul 25, 2020·Journal of the American Chemical Society·Collin G BorcikBenjamin J Wylie
Jun 29, 2021·Frontiers in Molecular Biosciences·Charline FagnenCatherine Vénien-Bryan
Aug 28, 2021·Frontiers in Molecular Biosciences·Michael BründlAnna Stary-Weinzinger
May 12, 2018·Journal of Chemical Theory and Computation·Karina OlesenHimanshu Khandelia

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Methods Mentioned

BETA
X-ray
PCA
FRET

Software Mentioned

gromacs
Swiss
PROPKA
membed
wham tool of gromacs
PdbViewer

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