Structural Biology & Biochemistry (SBB) Theme Seminar - 1) Pro-ferroptotic lipids as key regulators for caveola formation and disassembly; 2) Structural analysis of a pain-inducing peptide from the Australian stinging tree

When: Thursday 28 August at 10 am

Where: 50-T105 (Engineering building)

Speaker 1: Dr Yeping Wu (IMB)

Pro-ferroptotic lipids as key regulators for caveola formation and disassembly

Abstract: Caveolae are specialized plasma membrane domains with a unique lipid composition. Lipid peroxidation has recently been implicated in triggering caveola disassembly, releasing cavin proteins to regulate oxidative stress associated cellular processes, particularly ferroptosis. Here, we investigated how specific lipids influence caveola formation and their response to oxidative stress. A targeted screening of pro-ferroptotic enzymes identified ACSL4, a key enzyme in synthesizing polyunsaturated fatty acid (PUFA)-linked phospholipids, and ether phospholipid biosynthesis enzymes as critical regulators of caveola formation. Membrane-incorporated omega-6 PUFAs promoted caveola formation, while their displacement by omega-3 PUFAs or monounsaturated fatty acids disrupted this process. Importantly, oxidation of omega-6 PUFA chains in phosphatidylethanolamine (PE) triggered caveola disassembly during lipid peroxidation, potentially by affecting cavin-membrane interactions. These findings unveil a new model for caveola formation and signaling, linking caveola dynamics to ferroptosis with pro-ferroptotic lipids as essential caveolar components and key control points for caveola disassembly under oxidative stress.

Bio: Dr Yeping Wu received her PhD from University of Queensland and is currently a Postdoctoral Research Fellow at the Institute for Molecular Bioscience. Her research focuses on how caveolae, specialised membrane structures, sense and respond to stress conditions. She has uncovered how lipid peroxidation leads to caveola disassembly and regulates ferroptosis and the antioxidant response through NRF2 under oxidative stress. Her recent work reveals that pro-ferroptotic lipids are key regulators for caveola formation, linking caveola stability and dynamics to lipid metabolism. She applies advanced imaging and model systems to investigate how membrane behaviour influences cellular stress responses and cancer progression.

Speaker 2: Saipriyaa Vasan (AIBN)

Structural analysis of a pain-inducing peptide from the Australian stinging tree

Abstract: Gympietides are a recently discovered class of peptides from the venom of the Australian Stinging Tree that prolong pain by inhibiting the inactivation of voltage-gated sodium channels in sensory neurons. TMEM233, a previously uncharacterised transmembrane protein, was recently identified as a molecular target of gympietides and is a potential auxiliary sodium channel protein. In this study, we investigated the structure of the gympietide ExTxA (Dendrocnide excelsa toxin) in a membrane-mimicking environment using multidimensional heteronuclear NMR spectroscopy. We determined the 3D structure of isotope-labelled ExTxA in DPC micelles and observed a rearrangement of a hydrophobic amino acid loop compared to the previously reported structure in acetonitrile–water, suggesting a conformation adapted to the membrane environment. Given TMEM233’s short predicted extracellular domain, this loop is likely critical for membrane-mediated interactions with TMEM233. We further examined ExTxA’s binding to trichome-derived components and identified a strong interaction with a lipid transfer protein (LTP), forming a stable complex that enhances the toxin stability in aqueous environments and facilitate delivery to its target. Together, these findings provide new structural and mechanistic insights into ExTxA–TMEM233 interactions and the potential role of LTPs in the toxin’s lifecycle, advancing our understanding of pain modulation by gympietides.

Bio: Saipriyaa Vasan earned her Master’s in Biotechnology from Macquarie University in 2017, gaining research experience in cloning and recombinant protein expression before joining Murdoch University to work on breeding sterile Leucaena for Western Australia, refining her molecular biology expertise. She is currently pursuing a PhD at the University of Queensland investigating gympietide toxins from the Australian stinging tree to understand their modulation of sodium ion channels and role in pain pathways. Saipriyaa is skilled in protein biochemistry, molecular biology, and analytical techniques including HPLC, SEC, NMR spectroscopy, and mass spectrometry, and is passionate about advancing impactful, collaborative research.