Active fragments from pro- and antiapoptotic BCL-2 proteins have distinct membrane behavior reflecting their functional divergence

• Published in: PloS one Vol. 5; no. 2; p. e9066
• Main Authors: Guillemin, Yannis, Lopez, Jonathan, Gimenez, Diana, Fuertes, Gustavo, Valero, Juan Garcia, Blum, Loïc, Gonzalo, Philippe, Salgado, Jesùs, Girard-Egrot, Agnès, Aouacheria, Abdel
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.02.2010; Public Library of Science (PLoS)
• Subjects: Amino Acid Sequence; Amino acids; Analysis; Animals; Apoptosis; Bax protein; Bcl-2 protein; bcl-2-Associated X Protein - chemistry; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; Bcl-x protein; bcl-X Protein - chemistry; bcl-X Protein - metabolism; BH3 Interacting Domain Death Agonist Protein - chemistry; BH3 Interacting Domain Death Agonist Protein - metabolism; Biochemistry; Biochemistry, Molecular Biology; Biochemistry/Molecular Evolution; Biophysics/Membrane Proteins and Energy Transduction; Brewster angle; Cell Biology/Cellular Death and Stress Responses; Cell death; Cell Line; Cytochrome; Cytochromes c - secretion; Divergence; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; Fragmentation; Fragments; Helices; Homology; Humans; Hydrophobic and Hydrophilic Interactions; Kinases; Life Sciences; Lipid Bilayers - chemistry; Lipid Bilayers - metabolism; Membrane Lipids - chemistry; Membrane Lipids - metabolism; Membranes; Mice; Mice, Knockout; Microscopy; Microscopy - methods; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Molecular Sequence Data; Monomolecular films; Morphology; Optical properties; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Pore formation; Protein Binding; Proteins; Sequence Homology, Amino Acid; France
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0009066

The BCL-2 family of proteins includes pro- and antiapoptotic members acting by controlling the permeabilization of mitochondria. Although the association of these proteins with the outer mitochondrial membrane is crucial for their function, little is known about the characteristics of this interaction. Here, we followed a reductionist approach to clarify to what extent membrane-active regions of homologous BCL-2 family proteins contribute to their functional divergence. Using isolated mitochondria as well as model lipid Langmuir monolayers coupled with Brewster Angle Microscopy, we explored systematically and comparatively the membrane activity and membrane-peptide interactions of fragments derived from the central helical hairpin of BAX, BCL-xL and BID. The results show a connection between the differing abilities of the assayed peptide fragments to contact, insert, destabilize and porate membranes and the activity of their cognate proteins in programmed cell death. BCL-2 family-derived pore-forming helices thus represent structurally analogous, but functionally dissimilar membrane domains.