Helix orientations in membrane-associated Bcl-XL determined by 15N-solid-state NMR spectroscopy

摘要: Controlled cell death is fundamental to tissue hemostasis and apoptosis malfunctions can lead a wide range of diseases. Bcl-xL an anti-apoptotic protein the function which linked its reversible interaction with mitochondrial outer membranes. Its interfacial intermittent bilayer association makes prediction bound structure difficult without using methods able extract data from dynamic systems. Here we investigate associated oriented lipid bilayers at physiological pH solid-state NMR spectroscopy. The are consistent C-terminal transmembrane anchoring sequence average alignment remaining helices, i.e. including helices 5 6, approximately parallel membrane surface. Data several biophysical approaches confirm that after removal C-terminus interactions weak. In presence membranes still interact Bak BH3 domain peptide suggesting model where hydrophobic unfolds inserts into membrane. During this conformational change binding pocket becomes accessible for protein–protein whilst N-terminal region remains intact.