Interaction of the C-terminal domain of Bcl-2 family proteins with model membranes.
Bcl-2 family proteins are involved in the cell homeostasis by regulating programmed cell death. Some of these proteins promote apoptosis, while others inhibit the same process. The C-terminal hydrophobic domain of some of these proteins is predicted to be involved in anchoring them to a variety of cell membranes, such as mitochondrial, endoplasmic reticulum and nuclear membranes. We have used five synthetic peptides imitating the C-terminal domain from both anti-apoptotic (Bcl-2) and pro-apoptotic members (Bak, Bax, and two mutants of this last protein) of this family to study their interaction with model membranes. Some differences were detected in the interaction with these peptides. The addition of all the peptides to large unilamellar vesicles destabilized them and released encapsulated carboxyfluorescein to different degrees, so that fluidity and the increase in negative curvature favoured the extent in the release of carboxyfluorescein. Bcl-2-C and Bax-C peptides produced the highest release levels in most cases, while BaxS184K-C was the least efficient in this respect. These results indicate that these C-terminal domains are able to insert themselves in the membranes, each in a different way that is probably related with their different way which can be related to their differing locations within the cell and their different roles in regulating apoptosis.
Torrecillas
Alejandro
A
Departamento de Bioquímica y Biología Molecular (A), Facultad de Veterinaria, Universidad de Murcia, Apartado de Correos 4021, E-30080, Murcia, Spain.
Martínez-Senac
María M
MM
Ausili
Alessio
A
Corbalán-García
Senena
S
Gómez-Fernández
Juan C
JC
D000595:Amino Acid Sequence; D017209:Apoptosis; D005452:Fluoresceins / Q000737:chemistry; D005454:Fluorescence Polarization; D008563:Membrane Lipids / Q000737:chemistry*; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry*
D005452:Fluoresceins; D008563:Membrane Lipids; D019253:Proto-Oncogene Proteins c-bcl-2; C024098:6-carboxyfluorescein