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Vortrag von Fabio Lolicato

Vortragstitel: "The synergistic interplay of protein oligomerization and lipid sorting in cellular membrane remodeling"
Anlass: SFB - Seminar
Beginn: 23.10.2025, 16:15 Uhr
Ort: CellNanOs, 38/201

Über den Vortragenden: Dr. Fabio Lolicato forscht am Biochemiezentrum der Universität Heidelberg.

Many pore-forming proteins share common principles in their mechanisms of action. Typically, they begin as soluble domains that specifically interact with acidic lipids, followed by self-assembly into closed, membrane-associated structures. Two notable examples at the Plasma Membrane are Fibroblast Growth Factor 2 (FGF2) and Gasdermin-D (GSDM-D). FGF2 is a cell survival factor involved in tumor-associated angiogenesis and is secreted via an unconventional pathway that involves direct translocation across the plasma membrane. GSDM-D, on the other hand, plays a central role in pyroptosis by forming membrane pores that drive inflammatory cell death. Both proteins bind to the plasma membrane through specific protein–lipid interactions, with PI(4,5)P₂ serving as a key trigger for their dimerization and subsequent oligomerization. Using multiscale molecular dynamics simulations, we found that FGF2 and GSDM-D oligomers preferentially associate with lipids possessing high negative charge and intrinsic curvature, with more than 60% of the surrounding lipids classified as non-bilayer lipids. This selective lipid recruitment likely induces local phase transitions and charge asymmetries within the membrane, promoting destabilization. In the case of FGF2, such destabilization facilitates membrane pore opening and protein translocation, while for GSDM-D we propose to promote conformational rearrangements that enable membrane insertion and pore formation. We propose that the geometry of FGF2 and GSDM-D oligomers, together with their lipid-sorting capacity, is crucial for membrane destabilization. These findings suggest a unifying biophysical mechanism shared by diverse pore-forming proteins that assemble into ring-like structures.