Patra, Swarna M and Chakraborty, Sudip and Shahane, Ganesh and Prasanna, Xavier and Sengupta, Durba and Maiti, Prabal K and Chattopadhyay, Amitabha (2015) Differential dynamics of the serotonin(1A) receptor in membrane bilayers of varying cholesterol content revealed by all atom molecular dynamics simulation. In: MOLECULAR MEMBRANE BIOLOGY, 32 (4). pp. 127-137.
Full text not available from this repository. (Request a copy)Abstract
The serotonin(1A) receptor belongs to the superfamily of G protein-coupled receptors (GPCRs) and is a potential drug target in neuropsychiatric disorders. The receptor has been shown to require membrane cholesterol for its organization, dynamics and function. Although recent work suggests a close interaction of cholesterol with the receptor, the structural integrity of the serotonin(1A) receptor in the presence of cholesterol has not been explored. In this work, we have carried out all atom molecular dynamics simulations, totaling to 3s, to analyze the effect of cholesterol on the structure and dynamics of the serotonin(1A) receptor. Our results show that the presence of physiologically relevant concentration of membrane cholesterol alters conformational dynamics of the serotonin(1A) receptor and, on an average lowers conformational fluctuations. Our results show that, in general, transmembrane helix VII is most affected by the absence of membrane cholesterol. These results are in overall agreement with experimental data showing enhancement of GPCR stability in the presence of membrane cholesterol. Our results constitute a molecular level understanding of GPCR-cholesterol interaction, and represent an important step in our overall understanding of GPCR function in health and disease.
| Item Type: | Journal Article |
|---|---|
| Publication: | MOLECULAR MEMBRANE BIOLOGY |
| Publisher: | TAYLOR & FRANCIS LTD |
| Additional Information: | Copy right for this article belongs to the TAYLOR & FRANCIS LTD, 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND |
| Keywords: | GPCR; serotonin(1A) receptor; membrane cholesterol; molecular dynamics simulation |
| Department/Centre: | Division of Physical & Mathematical Sciences > Physics |
| Date Deposited: | 04 Mar 2016 06:06 |
| Last Modified: | 04 Mar 2016 06:06 |
| URI: | http://eprints.iisc.ac.in/id/eprint/53377 |
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