4S0O

Crystal Structure of the Autoinhibited Dimer of Pro-apoptotic BAX (I)

4S0O の概要

• エントリーDOI: 10.2210/pdb4s0o/pdb
• 関連するPDBエントリー: 1F16 4S0P
• 分子名称: Apoptosis regulator BAX (2 entities in total)
• 機能のキーワード: bcl-2 family protein, apoptosis regulator, autoinhibited dimer, apoptosis
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Isoform Alpha: Mitochondrion membrane; Single-pass membrane protein. Isoform Beta: Cytoplasm. Isoform Gamma: Cytoplasm. Isoform Delta: Cytoplasm : Q07812
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 42328.58

構造登録者

Priyadarshi, A.,Gavathiotis, E. (登録日: 2015-01-02, 公開日: 2016-07-20, 最終更新日: 2023-09-20)

主引用文献

Garner, T.P.,Reyna, D.E.,Priyadarshi, A.,Chen, H.C.,Li, S.,Wu, Y.,Ganesan, Y.T.,Malashkevich, V.N.,Almo, S.S.,Cheng, E.H.,Gavathiotis, E.
An Autoinhibited Dimeric Form of BAX Regulates the BAX Activation Pathway.
Mol.Cell, 63:485-497, 2016

PubMed Abstract: Pro-apoptotic BAX is a cell fate regulator playing an important role in cellular homeostasis and pathological cell death. BAX is predominantly localized in the cytosol, where it has a quiescent monomer conformation. Following a pro-apoptotic trigger, cytosolic BAX is activated and translocates to the mitochondria to initiate mitochondrial dysfunction and apoptosis. Here, cellular, biochemical, and structural data unexpectedly demonstrate that cytosolic BAX also has an inactive dimer conformation that regulates its activation. The full-length crystal structure of the inactive BAX dimer revealed an asymmetric interaction consistent with inhibition of the N-terminal conformational change of one protomer and the displacement of the C-terminal helix α9 of the second protomer. This autoinhibited BAX dimer dissociates to BAX monomers before BAX can be activated. Our data support a model whereby the degree of apoptosis induction is regulated by the conformation of cytosolic BAX and identify an unprecedented mechanism of cytosolic BAX inhibition.

PubMed: 27425408
DOI: 10.1016/j.molcel.2016.06.010

実験手法

X-RAY DIFFRACTION (1.9 Å)