The transmembrane domain of the SNARE protein VAMP2 is highly sensitive to its lipid environment

Abstract

Neurotransmitter and hormone exocytosis depends on SNARE protein transmembrane domains and membrane lipids but their interplay is poorly understood. We investigated the interaction of the structure of VAMP2, a vesicular transmembrane SNARE protein, and membrane lipid composition by infrared spectroscopy using either the wild-type transmembrane domain (TMD), VAMP2_TM22, or a peptide mutated at the central residues G₁₀₀/C₁₀₃ (VAMP2_TM22VV) previously identified by us as being critical for exocytosis. Our data show that the structure of VAMP2_TM22, in terms of α-helices and β-sheets is strongly influenced by peptide/lipid ratios, by lipid species including cholesterol and by membrane surface charges. Differences observed in acyl chain alignments further underscore the role of the two central small amino acid residues G₁₀₀/C₁₀₃ within the transmembrane domain during lipid rearrangements in membrane fusion.

Keywords: ATR-infrared spectroscopy; Cholesterol; Exocytosis; Phospholipids; SNARE proteins; Synaptobrevin.