Conformation of BCL-XL upon Membrane Integration. J Mol Biol 2015 Jul 03;427(13):2262-70
Date
03/04/2015Pubmed ID
25731750Pubmed Central ID
PMC4457587DOI
10.1016/j.jmb.2015.02.019Scopus ID
2-s2.0-84930085953 (requires institutional sign-in at Scopus site) 52 CitationsAbstract
BCL-XL is an anti-apoptotic BCL-2 family protein found both in the cytosol and bound to intracellular membranes. Structural studies of BCL-XL have advanced by deleting its hydrophobic C-terminus and adding detergents to enhance solubility. However, since the C-terminus is essential for function and detergents strongly affect structure and activity, the molecular mechanisms controlling intracellular localization and cytoprotective activity are incompletely understood. Here we describe the conformations and ligand binding activities of water-soluble and membrane-bound BCL-XL, with its complete C-terminus, in detergent-free environments. We show that the C-terminus interacts with a conserved surface groove in the water-soluble state of the protein and inserts across the phospholipid bilayer in the membrane-bound state. Contrary to current models, membrane binding does not induce a conformational change in the soluble domain and both states bind a known ligand with affinities that are modulated by the specific state of the protein.
Author List
Yao Y, Fujimoto LM, Hirshman N, Bobkov AA, Antignani A, Youle RJ, Marassi FMAuthor
Francesca M. Marassi PhD Chair, Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Apoptosis Regulatory ProteinsBinding Sites
Calorimetry
Cell Membrane
Detergents
Humans
Lipid Bilayers
Models, Molecular
Nuclear Magnetic Resonance, Biomolecular
Peptide Fragments
Phospholipids
Protein Conformation
Protein Folding
Protein Multimerization
Protein Structure, Tertiary
Solubility
bcl-X Protein
