Interfacial Binding Sites for Cholesterol on TRP Ion Channels

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 2019 Nov 2

PMID 31672270

Citations 7

Authors

Anthony G Lee

Affiliations

Soon will be listed here.

Abstract

Transient receptor potential (TRP) channels are members of a large family of ion channels located in membranes rich in cholesterol, some of whose functions are affected by the cholesterol content of the membrane. Here, cholesterol binding to TRPs is studied using a docking procedure that allows the transmembrane surface of a TRP to be swept rapidly for potential binding sites at the interfaces on the two sides of the membrane. Cholesterol docking poses determined in this way match 89% of the cholesterol hemisuccinate molecules in published TRP structures when cholesterol hemisuccinate molecules unlikely to represent typical bound cholesterols are excluded. TRPs are tetrameric, with large clefts at the interfaces between subunits; cholesterol poses are located in hollows, largely within these clefts. Comparison of cholesterol poses with phospholipid binding sites suggests that binding of cholesterol to a TRP need not result in displacement of phospholipid molecules from the TRP surface.

Citing Articles

Regulation of ThermoTRP Channels by PIP2 and Cholesterol.

Rosenbaum T, Morales-Lazaro S Adv Exp Med Biol. 2023; 1422:245-277.

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Exploring TRPC3 Interaction with Cholesterol through Coarse-Grained Molecular Dynamics Simulations.

Clarke A, Groschner K, Stockner T Biomolecules. 2022; 12(7).

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The role of cholesterol binding in the control of cholesterol by the Scap-Insig system.

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The constellation of cholesterol-dependent processes associated with SARS-CoV-2 infection.

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Relative Affinities of Protein-Cholesterol Interactions from Equilibrium Molecular Dynamics Simulations.

Ansell T, Curran L, Horrell M, Pipatpolkai T, Letham S, Song W J Chem Theory Comput. 2021; 17(10):6548-6558.

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