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RESEARCH PRODUCT
Active Fragments from Pro- and Antiapoptotic BCL-2 Proteins Have Distinct Membrane Behavior Reflecting Their Functional Divergence
Gustavo FuertesJuan G. ValeroYannis GuilleminAgnès Girard-egrotJonathan LopezJesus SalgadoPhilippe GonzaloDiana GimenezLoïc J. BlumAbdel Aouacheriasubject
Membrane lipidsLipid BilayersMolecular Sequence Databcl-X Proteinlcsh:MedicineApoptosisBiologyCell LineProtein–protein interactionMembrane LipidsMice03 medical and health sciences0302 clinical medicineProtein structureMembrane activityAnimalsHumansAmino Acid Sequence[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM]lcsh:ScienceLipid bilayerInner mitochondrial membranebcl-2-Associated X Protein030304 developmental biologyMice KnockoutMicroscopy0303 health sciencesMultidisciplinarySequence Homology Amino Acidlcsh:RCytochromes cCell Biology/Cellular Death and Stress ResponsesFibroblastsPeptide FragmentsMitochondriaCell biologyBiochemistry/Molecular EvolutionMembrane proteinBiophysics/Membrane Proteins and Energy Transductionlcsh:QHydrophobic and Hydrophilic Interactions030217 neurology & neurosurgeryFunctional divergenceResearch ArticleBH3 Interacting Domain Death Agonist ProteinProtein Bindingdescription
International audience; BACKGROUND: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.METHODOLOGY/PRINCIPAL FINDINGS: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.CONCLUSION/SIGNIFICANCE:BCL-2 family-derived pore-forming helices thus represent structurally analogous, but functionally dissimilar membrane domains.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-01-01 | PLoS ONE |