Identification of cholesterol binding sites in the serotonin(1A) receptor

TitleIdentification of cholesterol binding sites in the serotonin(1A) receptor
Publication TypeJournal Article
Year of Publication2012
AuthorsSengupta, D, Chattopadhyay, A
JournalJournal of Physical Chemistry B
Volume116
Issue43
Pagination12991-12996
Date PublishedNOV
ISSN1520-6106
Abstract

The serotonin(1A) receptor is a representative member of the G protein-coupled receptor (GPCR) superfamily and serves as an important drug target in the development of therapeutic agents for neuropsychiatric disorders. Previous work has shown the requirement of membrane cholesterol in the organization, dynamics, and function of the serotonin(1A) receptor. We show here that membrane cholesterol binds preferentially to certain sites on the serotonin(1A) receptor by performing multiple, long time scale MARTINI coarse-grain molecular dynamics simulations. Interestingly, our results identify the highly conserved cholesterol recognition/interaction amino acid consensus (CRAC) motif on transmembrane helix V as one of the sites with high cholesterol occupancy, thereby confirming its role as a putative cholesterol binding motif. These results represent the first direct evidence for membrane cholesterol binding to specific sites on the serotonin(1A) receptor and represent an important step in our overall understanding of GPCR function in health and disease.

DOI10.1021/jp309888u
Type of Journal (Indian or Foreign)Foreign
Impact Factor (IF)3.607
Divison category: 
Physical and Materials Chemistry