The structure of a potassium-selective ion channel reveals a hydrophobic gate regulating ion permeation

Patricia S. Langan; Venu Gopal Vandavasi; Wojciech Kopec; Brendan Sullivan; Pavel V. Afonne; Kevin L. Weiss; Bert L. De Groot; Leighton Coates

doi:10.1107/S2052252520008271

The structure of a potassium-selective ion channel reveals a hydrophobic gate regulating ion permeation

Patricia S. Langan, Venu Gopal Vandavasi, Wojciech Kopec, Brendan Sullivan, Pavel V. Afonne, Kevin L. Weiss, Bert L. De Groot, Leighton Coates

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Protein dynamics are essential to function. One example of this is the various gating mechanisms within ion channels, which are transmembrane proteins that act as gateways into the cell. Typical ion channels switch between an open and closed state via a conformational transition which is often triggered by an external stimulus, such as ligand binding or pH and voltage differences. The atomic resolution structure of a potassium-selective ion channel named NaK2K has allowed us to observe that a hydrophobic residue at the bottom of the selectivity filter, Phe92, appears in dual conformations. One of the two conformations of Phe92 restricts the diameter of the exit pore around the selectivity filter, limiting ion flow through the channel, while the other conformation of Phe92 provides a larger-diameter exit pore from the selectivity filter. Thus, it can be concluded that Phe92 acts as a hydrophobic gate, regulating the flow of ions through the selectivity filter.

Original language	English
Pages (from-to)	835-843
Number of pages	9
Journal	IUCrJ
Volume	7
DOIs	https://doi.org/10.1107/S2052252520008271
State	Published - 2020

Funding

Research at ORNL’s Spallation Neutron Source was sponsored by the Scientific User Facilities Division, Office of Basic Energy Sciences, US Department of Energy (DOE). The Office of Biological and Environmental Research supported research at Oak Ridge National Laboratory’s Center for Structural Molecular Biology (CSMB) using facilities supported by the Scientific User Facilities Division, Office of Basic Energy Sciences, US Department of Energy. Results shown in this report are derived from work performed at Argonne National Laboratory (ANL), Structural Biology Center at the Advanced Photon Source. ANL is operated by UChicago Argonne, LLC, for the US Department of Energy, Office of Biological and Environmental Research, under Contract No. DE-AC02-06CH11357. PVA acknowledges support by the NIH (grant GM063210), the Phenix Industrial Consortium and the US Department of Energy under Contract No. DE-AC02-05CH11231 and BS acknowledges support by the NIH (R01-GM071939). WK and BLdG gratefully acknowledge funding from the German Research Foundation DFG through FOR 2518 DynIon, project P5.

Funders	Funder number
German Research Foundation DFG	FOR 2518 DynIon
Oak Ridge National Laboratory
Office of Basic Energy Sciences
Office of Biological and Environmental Research
Phenix Industrial Consortium	DE-AC02-05CH11231, R01-GM071939
Scientific User Facilities Division
US Department of Energy
National Institutes of Health	GM063210
U.S. Department of Energy
Basic Energy Sciences
Canadian Society for Molecular Biosciences

Keywords

Conformational transitions
Gating
Potassium ion channels
X-ray crystallography

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10.1107/S2052252520008271

Cite this

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title = "The structure of a potassium-selective ion channel reveals a hydrophobic gate regulating ion permeation",

abstract = "Protein dynamics are essential to function. One example of this is the various gating mechanisms within ion channels, which are transmembrane proteins that act as gateways into the cell. Typical ion channels switch between an open and closed state via a conformational transition which is often triggered by an external stimulus, such as ligand binding or pH and voltage differences. The atomic resolution structure of a potassium-selective ion channel named NaK2K has allowed us to observe that a hydrophobic residue at the bottom of the selectivity filter, Phe92, appears in dual conformations. One of the two conformations of Phe92 restricts the diameter of the exit pore around the selectivity filter, limiting ion flow through the channel, while the other conformation of Phe92 provides a larger-diameter exit pore from the selectivity filter. Thus, it can be concluded that Phe92 acts as a hydrophobic gate, regulating the flow of ions through the selectivity filter.",

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AU - Langan, Patricia S.

AU - Vandavasi, Venu Gopal

AU - Kopec, Wojciech

AU - Sullivan, Brendan

AU - Afonne, Pavel V.

AU - Weiss, Kevin L.

AU - De Groot, Bert L.

AU - Coates, Leighton

PY - 2020

Y1 - 2020

N2 - Protein dynamics are essential to function. One example of this is the various gating mechanisms within ion channels, which are transmembrane proteins that act as gateways into the cell. Typical ion channels switch between an open and closed state via a conformational transition which is often triggered by an external stimulus, such as ligand binding or pH and voltage differences. The atomic resolution structure of a potassium-selective ion channel named NaK2K has allowed us to observe that a hydrophobic residue at the bottom of the selectivity filter, Phe92, appears in dual conformations. One of the two conformations of Phe92 restricts the diameter of the exit pore around the selectivity filter, limiting ion flow through the channel, while the other conformation of Phe92 provides a larger-diameter exit pore from the selectivity filter. Thus, it can be concluded that Phe92 acts as a hydrophobic gate, regulating the flow of ions through the selectivity filter.

AB - Protein dynamics are essential to function. One example of this is the various gating mechanisms within ion channels, which are transmembrane proteins that act as gateways into the cell. Typical ion channels switch between an open and closed state via a conformational transition which is often triggered by an external stimulus, such as ligand binding or pH and voltage differences. The atomic resolution structure of a potassium-selective ion channel named NaK2K has allowed us to observe that a hydrophobic residue at the bottom of the selectivity filter, Phe92, appears in dual conformations. One of the two conformations of Phe92 restricts the diameter of the exit pore around the selectivity filter, limiting ion flow through the channel, while the other conformation of Phe92 provides a larger-diameter exit pore from the selectivity filter. Thus, it can be concluded that Phe92 acts as a hydrophobic gate, regulating the flow of ions through the selectivity filter.

KW - Conformational transitions

KW - Gating

KW - Potassium ion channels

KW - X-ray crystallography

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The structure of a potassium-selective ion channel reveals a hydrophobic gate regulating ion permeation

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