SMBP Group Meeting: Sarah Rouse (Imperial College London)

Tuesday Aug 13, 2024, 2:00 PM → 6:00 PM America/New_York

3rd Floor Classroom (162 Fifth Avenue)

You are invited to the SMBp Group Meeting:


Speaker: Sarah Rouse (Imperial College London)

Topic: Characterising dynamic lipid-protein interactions from protein to membrane scales

Abstract: Specific protein-lipid interactions, referred to as the paralipidome and/or lipid fingerprints, play key roles in regulating cellular functions such as signaling, membrane trafficking, and structural stability. Understanding the paralipidome reveals how lipids influence protein function and localization, providing insights into disease mechanisms and therapeutic targets. This understanding may be particularly relevant for Class B1 GPCRs, with GLP-1R the target of peptide-based diabetes and obesity drugs. These current therapies have limitations, and there is a need to develop novel small molecules, including allosteric modulators, to finely tune receptor outputs. GPCR-lipid binding sites may represent an untapped opportunity for allosteric small molecule drug development. Our molecular simulation study of all 15 Class B1 family members in model plasma membranes uncovers specific lipid interactions, including the state-dependent modulation of the extracellular domain by the ganglioside lipid GM3, as well as state-dependent cholesterol binding. Beyond molecular level details of protein-lipid interactions, we aim to understand lipid-protein interactions in the broader context of membrane remodelling processes, such as the initial stages of parasite- and virus-host cell interactions and protein-mediated mitochondrial inner membrane fusion.