Date of Award

August 2020

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biomedical and Chemical Engineering

Advisor(s)

Shikha Nangia

Keywords

Cholesterol, Energy, GPCR, oligomerization, PANEL, S1P1

Subject Categories

Engineering

Abstract

G-protein-coupled receptors (GPCRs) are the most diverse membrane proteins in eukaryotes that transmit chemical signals to the cell. GPCRs are considered the largest family of targets for approved drugs on the market. Sphingosine 1-phosphate receptor 1 (S1P1), a widely expressed GPCR protein in many cell types, performs signal transduction function not only in the monomeric state but also in the dimeric or complex oligomeric states. However, the detail of the S1P1 assembly is still not clearly understood. Cholesterol is believed to affect S1P1 dimerization, but the details of the cholesterol-binding sites with S1P1 are not well understood. In this project, we employ the recently developed Protein AssociatioN Energy Landscape (PANEL) method to investigate S1P1 dimer formation in cholesterol containing membrane. The results of this study can be used to drive theoretical and experimental trials in the study of GPCR oligomers, as well as in the study of transmembrane protein - protein interactions in general.

Access

Open Access

Included in

Engineering Commons

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