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Speaker: Edward Lyman (University of Delaware)
Topic: How are membranes and their proteins matched?
Abstract: Membranes and their lipidomes vary substantially — across the tree of life, among the different cells of a metazoan, and between the different membranes within a single eukaryotic cell. The lipid composition of a membrane and how those lipids are distributed determines the structural and physico-chemical properties of the membrane, which are adapted to support particular functions. For example, the membrane of the endoplasmic reticulum is simple, loosely packed, and deformable, facilitating folding and insertion of membrane proteins during synthesis, while the plasma membrane features a complex mixture of lipids and cholesterol, distributed asymmetrically between the two leaflets. In this talk, I will discuss our recent efforts to determine the asymmetric distribution of lipids in mammalian plasma membranes,1 and how this asymmetry (and its loss) might couple to signaling in the GPCR family. This function is mediated by a conserved PS-interaction motif on the cytoplasmic leaflet,2 which is a particular case of the more general question: How are membranes and their proteins matched? I will finish by discussing our recent efforts to address this question more generally, by training graph neural network representations of membrane proteins. By leveraging proteome-wide structure databases, we hope to uncover rules for membrane proteins across the tree of life.
[1] Lorent, J.H.; Ganesan, L.; Rivera-Longsworth, G.; Sezgin, E.; Levental, K.R.; Lyman, E.; Levental, I. “The molecular and structural asymmetry of the plasma membrane” Nature Chemical Biology 16:644 (2020)
[2] Thakur, N; Ray, AP; Sharp, L; Jin, B; Duong, A; Pour, NG; Obeng, S; Wijesekara, AV; Gao, Z-G; McCurdy, CR; Jacobson, KA; Lyman, E; Eddy, MT “Anionic phospholipids control mechanisms of GPCR-G protein recognition” Nat. Comm. 14:794(2023)