title: Conformational changes in BID, a pro-apoptotic BCL-2 family member, upon membrane binding. A site-directed spin labeling study.
abstract: The BCL-2 family proteins constitute a critical control point in apoptosis. BCL-2 family proteins display structural homology to channel-forming bacterial toxins, such as colicins, transmembrane domain of diphtheria toxin, and the N-terminal domain of delta-endotoxin. By analogy, it has been hypothesized the BCL-2 family proteins would unfold and insert into the lipid bilayer upon membrane association. We applied the site-directed spin labeling method of electron paramagnetic resonance spectroscopy to the pro-apoptotic member BID. Here we show that helices 6-8 maintain an alpha-helical conformation in membranes with a lipid composition resembling mitochondrial outer membrane contact sites. However, unlike colicins and the transmembrane domain of diphtheria toxin, these helices of BID are bound to the lipid bilayer without adopting a transmembrane orientation. Our study presents a more detailed model for the reorganization of the structure of tBID on membranes.
authors.affiliation: Howard Hughes Medical Institute, the Department of Pathology and Medicine, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Kyoung Joon
authors.initials: KJ
authors.lastname: Oh
authors.forename: Scott
authors.initials: S
authors.lastname: Barbuto
authors.forename: Natalie
authors.initials: N
authors.lastname: Meyer
authors.forename: Ryung-Suk
authors.initials: RS
authors.lastname: Kim
authors.forename: R John
authors.initials: RJ
authors.lastname: Collier
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Korsmeyer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D013113:Spin Labels
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; C494815:Bid protein, mouse; D002352:Carrier Proteins; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D013113:Spin Labels