A Diazirine‐Modified Membrane Lipid to Study Peptide/Lipid Interactions – Chances and Challenges. Issue 59 (28th September 2021)

• Record Type: Journal Article
• Authors: Dorner, Julia; Korn, Patricia; Gruhle, Kai; Ramsbeck, Daniel; Garamus, Vasil M.; Lilie, Hauke; Meister, Annette; Schwieger, Christian; Ihling, Christian; Sinz, Andrea; Drescher, Simon
• Is Part Of: Chemistry. Volume 27:Issue 59(2021)
• Page Start: 14586
• Page End: 14593
• Publication Date: 2021-09-28
• Subjects: diazirine -- mass spectrometry -- membrane lipids -- miscibility -- peptide/lipid interactions -- photo-cross-linking -- XL-MS; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202102048
• Languages: English
• ISSNs: 0947-6539

Abstract

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. Abstract : Can diazirine‐modified lipids be used to locate the position of UV‐induced cross‐links between this lipid and a membrane peptide by using MS? Although DiazPC fulfils all prerequisites for a photo‐activatable membrane lipid to study protein/lipid interactions and the cross‐links can be exactly assigned, we observed a backfolding of the lipid's alkyl chain. This is a general phenomenon for any type of membrane lipids with a hydrophilic group in the alkyl chain.