On the impact of non-covalent interactions on the formation of protein-lipid complexes in the gas phase and in solution

Abstract

This thesis explores protein-lipid interactions of the antimicrobial peptide LL-37, supercharged variants of LL-37 as well as the Ca2+-sensor protein Synptotagmin-1 (Syt1) by mass spectrometry (MS) and other techniques. Studying the LL-37 wild-type revealed that electrostatic interactions determine the ion intensity and the gas-phase stability of the complexes during native MS, while the hydrophobic effect in solution contributes to their ion intensity. Investigating the interactions of supercharged LL-37 variants by native MS demonstrated that the surface charge affects the lipid preferences. Finally, native MS, biophysical techniques and MD simulations were employed to characterise the Ca2+-dependent lipid preferences of Syt1, showing a preference for negatively charged lipids and elucidating its membrane-binding mechanism. Overall, this thesis contributes to the general understanding of how non-covalent interactions impact protein-lipid interactions.