8GSV

Crystal structure of human BAK in complex with the Pxt1 BH3 domain

Summary for 8GSV

• Entry DOI: 10.2210/pdb8gsv/pdb
• Descriptor: Bcl-2 homologous antagonist/killer, Peroxisomal testis-specific protein 1 (3 entities in total)
• Functional Keywords: peroxisomal testis-specific 1, pxt1, bak, bh3, apoptosis
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 24
• Total formula weight: 267204.73

Authors

Lim, D.,Ku, B. (deposition date: 2022-09-07, release date: 2023-05-10, Last modification date: 2023-11-29)

Primary citation

Lim, D.,Choe, S.H.,Jin, S.,Lee, S.,Kim, Y.,Shin, H.C.,Choi, J.S.,Oh, D.B.,Kim, S.J.,Seo, J.,Ku, B.
Structural basis for proapoptotic activation of Bak by the noncanonical BH3-only protein Pxt1.
Plos Biol., 21:e3002156-e3002156, 2023

PubMed Abstract: Bak is a critical executor of apoptosis belonging to the Bcl-2 protein family. Bak contains a hydrophobic groove where the BH3 domain of 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 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.

PubMed: 37315086
DOI: 10.1371/journal.pbio.3002156

Experimental method

X-RAY DIFFRACTION (2.2 Å)