5UA4

Crystal structure of A179L:Bid BH3 complex

5UA4 の概要

• エントリーDOI: 10.2210/pdb5ua4/pdb
• 関連するPDBエントリー: 5UA5
• 分子名称: 5-HL, BH3-interacting domain death agonist (3 entities in total)
• 機能のキーワード: apoptosis, bcl-2
• 由来する生物種: African swine fever virus (ASFV); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 21539.57

構造登録者

Banjara, S.,Caria, S.,Kvansakul, M. (登録日: 2016-12-18, 公開日: 2017-01-04, 最終更新日: 2024-03-06)

主引用文献

Banjara, S.,Caria, S.,Dixon, L.K.,Hinds, M.G.,Kvansakul, M.
Structural Insight into African Swine Fever Virus A179L-Mediated Inhibition of Apoptosis.
J. Virol., 91:-, 2017

PubMed Abstract: Programmed cell death is a tightly controlled process critical for the removal of damaged or infected cells. Pro- and antiapoptotic proteins of the Bcl-2 family are pivotal mediators of this process. African swine fever virus (ASFV) is a large DNA virus, the only member of the family, and harbors A179L, a putative Bcl-2 like protein. A179L has been shown to bind to several proapoptotic Bcl-2 proteins; however, the hierarchy of binding and the structural basis for apoptosis inhibition are currently not understood. We systematically evaluated the ability of A179L to bind proapoptotic Bcl-2 family members and show that A179L is the first antiapoptotic Bcl-2 protein to bind to all major death-inducing mammalian Bcl-2 proteins. We then defined the structural basis for apoptosis inhibition of A179L by determining the crystal structures of A179L bound to both Bid and Bax BH3 motifs. Our findings provide a mechanistic understanding for the potent antiapoptotic activity of A179L by identifying it as the first panprodeath Bcl-2 binder and serve as a platform for more-detailed investigations into the role of A179L during ASFV infection. Numerous viruses have acquired strategies to subvert apoptosis by encoding proteins capable of sequestering proapoptotic host proteins. African swine fever virus (ASFV), a large DNA virus and the only member of the family, encodes the protein A179L, which functions to prevent apoptosis. We show that A179L is unusual among antiapoptotic Bcl-2 proteins in being able to physically bind to all core death-inducing mammalian Bcl-2 proteins. Currently, little is known regarding the molecular interactions between A179L and the proapoptotic Bcl-2 members. Using the crystal structures of A179L bound to two of the identified proapoptotic Bcl-2 proteins, Bid and Bax, we now provide a three-dimensional (3D) view of how A179L sequesters host proapoptotic proteins, which is crucial for subverting premature host cell apoptosis.

PubMed: 28053104
DOI: 10.1128/JVI.02228-16

実験手法

X-RAY DIFFRACTION (2.6 Å)