Conversion of Bim-BH3 from Activator to Inhibitor of Bak through Structure-Based Design.
Mol Cell
; 68(4): 659-672.e9, 2017 Nov 16.
Article
em En
| MEDLINE
| ID: mdl-29149594
ABSTRACT
Certain BH3-only proteins transiently bind and activate Bak and Bax, initiating their oligomerization and the permeabilization of the mitochondrial outer membrane, a pivotal step in the mitochondrial pathway to apoptosis. Here we describe the first crystal structures of an activator BH3 peptide bound to Bak and illustrate their use in the design of BH3 derivatives capable of inhibiting human Bak on mitochondria. These BH3 derivatives compete for the activation site at the canonical groove, are the first engineered inhibitors of Bak activation, and support the role of key conformational transitions associated with Bak activation.
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MEDLINE
Assunto principal:
Peptídeos
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Apoptose
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Proteína Killer-Antagonista Homóloga a bcl-2
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Proteína 11 Semelhante a Bcl-2
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Mitocôndrias
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article