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 Jjournal_title
Biophysical journalauthors
Lee AGdoi
10.1016/j.bpj.2019.10.011subject
Has Abstractpub_date
2019-11-19 00:00:00pages
2020-2033issue
10eissn
0006-3495issn
1542-0086pii
S0006-3495(19)30858-6journal_volume
117pub_type
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