OxTalks will soon move to the new Halo platform and will become 'Oxford Events.' There will be a need for an OxTalks freeze. This was previously planned for Friday 14th November – a new date will be shared as soon as it is available (full details will be available on the Staff Gateway).
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The membranes of cells from across the tree of life have evolved complex lipidomes — many di7erent
chemical species, in many cases distributed asymmetrically between the two leaflets of the membrane.
Lipid composition and how those lipids are distributed determine the structural and chemical properties
of the membrane, which have adapted and are regulated to support function. I will present work from a
recent collaboration to determine the asymmetric distribution of lipids in mammalian plasma
membranes,1 and a new model that links rapid cholesterol flip-flop to regulated loss of lipid
asymmetry.2 I will use a specific example from the GPCR family to illustrate how asymmetry (and its loss)
might couple to signaling. This mechanism is mediated by a conserved PS-interaction motif on the
cytoplasmic leaflet,3 which is a particular case of the more general question: How are membranes and
their proteins matched? I will finish by discussing our recent e7orts to address this question more generally,
by training machine learning models which predict membrane localization of membrane proteins from
sequence or structure. By leveraging proteome-wide databases, we hope to uncover new 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] Doktorova, M; Symons, J.L.; Zhang, X.; Wang, H-Y.; Schlegel, Jan; Lorent, J.H.; Heberle, F.A.; Sezgin, E. Lyman, E.; Levental, K.R.;
Levental, I. “Cell membranes sustain phospholipid imbalance via cholesterol asymmetry,” accepted to Cell
[3] 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)
