MicroED structure of the NaK ion channel reveals a Na+ partition process into the selectivity filter.

Communications Biology
Shian Liu, T Gonen

Abstract

Sodium (Na+) is a ubiquitous and important inorganic salt mediating many critical biological processes such as neuronal excitation, signaling, and facilitation of various transporters. The hydration states of Na+ are proposed to play critical roles in determining the conductance and the selectivity of Na+ channels, yet they are rarely captured by conventional structural biology means. Here we use the emerging cryo-electron microscopy (cryoEM) method micro-electron diffraction (MicroED) to study the structure of a prototypical tetrameric Na+-conducting channel, NaK, to 2.5 Å resolution from nano-crystals. Two new conformations at the external site of NaK are identified, allowing us to visualize a partially hydrated Na+ ion at the entrance of the channel pore. A process of dilation coupled with Na+ movement is identified leading to valuable insights into the mechanism of ion conduction and gating. This study lays the ground work for future studies using MicroED in membrane protein biophysics.

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Citations

May 2, 2019·Nature Methods·Brent L Nannenga, Tamir Gonen
Jan 9, 2019·Frontiers in Molecular Biosciences·Brent L NannengaDan Shi
Aug 29, 2019·Science Advances·Hongyi XuMartin Högbom
Aug 28, 2020·Frontiers in Molecular Biosciences·Emma V BealePeijun Zhang
Nov 11, 2020·Biochemical Society Transactions·Tristan O C KwanIsabel Moraes
Dec 10, 2020·Proceedings of the National Academy of Sciences of the United States of America·Michael W MartynowyczTamir Gonen
Jan 26, 2021·Frontiers in Molecular Biosciences·Patrick R GleasonJeremy H Mills
Dec 31, 2020·International Journal of Molecular Sciences·Johannes Thoma, Björn M Burmann
Mar 2, 2021·Acta Crystallographica. Section D, Structural Biology·Max T B Clabbers, Hongyi Xu
Apr 1, 2019·Journal of Structural Biology·Koji YonekuraSaori Maki-Yonekura
Mar 25, 2021·Emerging Topics in Life Sciences·Anshul AssaiyaJanesh Kumar
Feb 6, 2020·Structure·Michael W MartynowyczTamir Gonen
Jun 22, 2021·Annual Review of Biochemistry·Xuelang MuTamir Gonen
Dec 18, 2018·ACS Central Science·Christopher G JonesTamir Gonen
Sep 1, 2021·Proceedings of the National Academy of Sciences of the United States of America·Michael W MartynowyczTamir Gonen
Oct 30, 2021·Nature Communications·Adam LewisKatherine Henzler-Wildman

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Methods Mentioned

BETA
X-ray
electron diffraction
electron microscopy

Software Mentioned

CCP4i
refine
iMOSFLM
phenix
AIMLESS
sftools
MicroED

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