Interfacial Binding Sites for Cholesterol on TRP Ion Channels.

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.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Lee AG

doi

10.1016/j.bpj.2019.10.011

subject

Has Abstract

pub_date

2019-11-19 00:00:00

pages

2020-2033

issue

10

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(19)30858-6

journal_volume

117

pub_type

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