A Diazirine-Modified Membrane Lipid to Study Peptide/Lipid Interactions – Chances and Challenges

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Abstract

Although incorporation of photo-activatable lipids into membranes potentially opens up novel avenues for investigating interactions with proteins, the question of whether diazirine-modified lipids are suitable for such studies, remains under debate. Focusing on the potential for studying lipid/peptide interactions by cross-linking mass spectrometry (XL-MS), we developed a diazirine-modified lipid (DiazPC), and examined its behaviour in membranes incorporating the model α-helical peptide LAVA20. We observed an unexpected backfolding of the diazirine-containing stearoyl chain of the lipid. This surprising behaviour challenges the potential application of DiazPC for future XL-MS studies of peptide and protein/lipid interactions. The observations made for DiazPC most likely represent a general phenomenon for any type of membrane lipids with a polar moiety incorporated into the alkyl chain. Our finding is therefore of importance for future protein/lipid interaction studies relying on modified lipid probes.

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Dorner, J., Korn, P., Gruhle, K., Ramsbeck, D., Garamus, V. M., Lilie, H., … Drescher, S. (2021). A Diazirine-Modified Membrane Lipid to Study Peptide/Lipid Interactions – Chances and Challenges. Chemistry - A European Journal, 27(59), 14586–14593. https://doi.org/10.1002/chem.202102048

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