Hydrophobic Mismatch Modulates Stability and Plasticity of Human Mitochondrial VDAC2

摘要: The human mitochondrial outer membrane protein voltage-dependent anion channel isoform 2 (hVDAC2) is a β-barrel metabolite flux that indispensable for cell survival. It well established physical forces imposed on transmembrane by its surrounding lipid environment decide structure and stability. Yet, how the protein-lipid interplay together regulate hVDAC2 stability unknown. Here, we combine experimental biophysical investigations of with all-atom molecular dynamics simulations to study effect most abundant phosphocholine (PC) lipids hVDAC2. We demonstrate experimentally increasing PC acyl chain length from diC14:0 diC18:0-PC has nonlinear β-barrel. show highest in diC16:0-PC, which exhibits negative mismatch barrel. Our also reveal structural rigidity under optimal provided diC16:0-PC bilayers. Further, validate our observations altering properties membranes indirectly using cholesterol. propose VDAC plasticity are modulated bilayer.