In:
PLOS Biology, Public Library of Science (PLoS), Vol. 21, No. 6 ( 2023-6-14), p. e3002156-
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.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3002156
DOI:
10.1371/journal.pbio.3002156.g001
DOI:
10.1371/journal.pbio.3002156.g002
DOI:
10.1371/journal.pbio.3002156.g003
DOI:
10.1371/journal.pbio.3002156.g004
DOI:
10.1371/journal.pbio.3002156.g005
DOI:
10.1371/journal.pbio.3002156.g006
DOI:
10.1371/journal.pbio.3002156.g007
DOI:
10.1371/journal.pbio.3002156.g008
DOI:
10.1371/journal.pbio.3002156.s001
DOI:
10.1371/journal.pbio.3002156.s002
DOI:
10.1371/journal.pbio.3002156.s003
DOI:
10.1371/journal.pbio.3002156.s004
DOI:
10.1371/journal.pbio.3002156.s005
DOI:
10.1371/journal.pbio.3002156.s006
DOI:
10.1371/journal.pbio.3002156.s007
DOI:
10.1371/journal.pbio.3002156.s008
DOI:
10.1371/journal.pbio.3002156.s009
DOI:
10.1371/journal.pbio.3002156.s010
DOI:
10.1371/journal.pbio.3002156.s011
DOI:
10.1371/journal.pbio.3002156.s012
DOI:
10.1371/journal.pbio.3002156.s013
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2126773-X
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