Structural basis for proapoptotic activation of Bak by the noncanonical BH3-only protein Pxt1.

Structural basis for proapoptotic activation of Bak by the noncanonical BH3-only protein Pxt1.

Blog Article

Bak is a critical executor of apoptosis belonging to the Bcl-2 protein family.Bak contains a hydrophobic groove where the BH3 domain of Womens Sandals proapoptotic Bcl-2 family members can be accommodated, which initiates its activation.Once activated, Bak undergoes a conformational change to oligomerize, which leads to mitochondrial destabilization and the release of cytochrome c into the cytosol and eventual apoptotic cell death.

In this study, we investigated the molecular aspects and functional consequences of the interaction between Bak and peroxisomal testis-specific 1 (Pxt1), a noncanonical BH3-only protein exclusively expressed in the testis.Together with various biochemical approaches, this interaction was verified and analyzed at the atomic level by determining the crystal structure of the Bak-Pxt1 BH3 complex.In-depth biochemical and cellular analyses demonstrated that Pxt1 functions as a Bak-activating proapoptotic factor, and its Cocktail Napkins BH3 domain, which mediates direct intermolecular interaction with Bak, plays a critical role in triggering apoptosis.

Therefore, this study provides a molecular basis for the Pxt1-mediated novel pathway for the activation of apoptosis and expands our understanding of the cell death signaling coordinated by diverse BH3 domain-containing proteins.