Biophysical effect of lipid modification at palmitoylation site on the structure of Caveolin 3

Caveolae are small plasma membrane invaginations that play many roles in signal transduction, endocytosis, mechanoprotection, lipid metabolism. The most important protein in caveolae is the integral membrane protein, caveolin, which is divided into three families such as caveolin 1, caveolin 2, and caveolin 3. Caveolin 1 and 3 are known to incorporate palmitate through linkage to three cysteine residues. Regulation of the protein palmitoylation cycle is important for the cellular processes such as intracellular localization of the target protein, membrane association, conformation, protein-protein interaction, and activity. However, the detailed aspect of individual palmitoylation has not been studied. In the present work, the role of each lipid modification at three cysteines was studied by NMR. Our results suggest that each lipid modification at the natively palmitoylation site has its own roles. For example, lipidations to C106 and C129 are play a role in structural stabilization, however, interestingly, lipid modification to C116 interrupts the structural stabilization.