Lipid Research Division Seminar Series

Membrane matters: Mapping the conformational landscape of PI3K⍺ activation on lipid bilayers
Hayarpi Torosyan, University of California, San Francisco

This presentation will define the structural basis of PI3Kα activation, integrating the lipid bilayer, Ras GTPases, and RTK-derived phosphopeptides. It is aimed at researchers interested in cell signaling, structural biology, membrane biochemistry and cancer biology. Key takeaways include the stepwise relief of PI3Kα autoinhibition by the lipid bilayer and PIP2, the cooperative role of Ras and RTK inputs, and the discovery of an active, signaling-competent PI3Kα dimer that amplifies downstream Akt signaling.

MprF from antimicrobial resistant pathogens is a promiscuous lipid scramblase with broad substrate specificity
Matthew Hankins, University of Oxford

MprF provides many bacteria with increased resistance to antimicrobials by modifying inner leaflet lipid headgroups, and translocating modified lipid to the outer leaflet. MprF presents a novel target in multiresistant pathogens, but structural information is limited and the mechanism of lipid transport is poorly understood. Here, we present the cryo-EM structure of MprF from P. aeruginosa (PaMprF). PaMprF adopts an ‘open’ conformation with a lipid-exposed groove on the periplasmic side. We demonstrate that PaMprF translocates a wide range of different lipids without an external energy source. This suggests that PaMprF is the first dedicated lipid scramblase to be characterised in bacteria.