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A Structural Model for Bax?2-Mediated Activation of Caspase 8-Dependent Apoptosis.

ABSTRACT: Bax?2 is a pro-apoptotic anti-tumor protein in the Bax family. While most of the Bax family causes cell death by targeting mitochondria, Bax?2 forms cytosolic aggregates and activates caspase 8-dependent cell death. We previously showed that the Bax?2 helix ?9 is critical for caspase 8 recruitment. However, the interaction between these two proteins at the structural level is unknown. In this in silico study, we performed molecular dynamics (MD) simulations and protein-protein docking on Bax?2 variants. The results suggest that the Bax?2 variants have different stable states. Mutating the Bax? mitochondria-targeting signal [L26P/L27P] appears to introduce a kink into helix ?1. Protein-protein docking suggests that helices ?9 of both wild-type Bax?2 and Bax?2 caspase 8 binding-deficient mutant [L164P] can fit in the same caspase 8 binding site, but the mutant is unable to fit as well as wild-type Bax?2. Together, these data point to a structural basis for explaining Bax?2 function in caspase 8-dependent cell death.

SUBMITTER: Xie B

PROVIDER: S-EPMC7432750 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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A Structural Model for Bax∆2-Mediated Activation of Caspase 8-Dependent Apoptosis.

Xie Bing B Yao Qi Q Xiang Jialing J Minh David D L DDL

International journal of molecular sciences 20200731 15

Bax∆2 is a pro-apoptotic anti-tumor protein in the Bax family. While most of the Bax family causes cell death by targeting mitochondria, Bax∆2 forms cytosolic aggregates and activates caspase 8-dependent cell death. We previously showed that the Bax∆2 helix α9 is critical for caspase 8 recruitment. However, the interaction between these two proteins at the structural level is unknown. In this in silico study, we performed molecular dynamics (MD) simulations and protein-protein docking on Bax∆2 v ...[more]

PMID: 32751845

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Dataset Information

A Structural Model for Bax?2-Mediated Activation of Caspase 8-Dependent Apoptosis.

Publications

A Structural Model for Bax∆2-Mediated Activation of Caspase 8-Dependent Apoptosis.

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