4UF2

Deerpox virus DPV022 in complex with Bax BH3

4UF2 の概要

• エントリーDOI: 10.2210/pdb4uf2/pdb
• 関連するPDBエントリー: 4UF1 4UF3
• 分子名称: Antiapoptotic membrane protein, Apoptosis regulator BAX (2 entities in total)
• 機能のキーワード: viral protein, deerpox virus, apoptosis, bcl-2, bax bh3
• 由来する生物種: Deerpox virus (strain W-1170-84) (DPV); 詳細
• 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: 22785.82

構造登録者

Burton, D.R.,Kvansakul, M. (登録日: 2014-12-23, 公開日: 2015-08-05, 最終更新日: 2024-05-01)

主引用文献

Burton, D.R.,Caria, S.,Marshall, B.,Barry, M.,Kvansakul, M.
Structural Basis of Deerpox Virus-Mediated Inhibition of Apoptosis.
Acta Crystallogr.,Sect.D, 71:1593-, 2015

PubMed Abstract: Apoptosis is a key innate defence mechanism to eliminate virally infected cells. To counteract premature host-cell apoptosis, poxviruses have evolved numerous molecular strategies, including the use of Bcl-2 proteins, to ensure their own survival. Here, it is reported that the Deerpox virus inhibitor of apoptosis, DPV022, only engages a highly restricted set of death-inducing Bcl-2 proteins, including Bim, Bax and Bak, with modest affinities. Structural analysis reveals that DPV022 adopts a Bcl-2 fold with a dimeric domain-swapped topology and binds pro-death Bcl-2 proteins via two conserved ligand-binding grooves found on opposite sides of the dimer. Structures of DPV022 bound to Bim, Bak and Bax BH3 domains reveal that a partial obstruction of the binding groove is likely to be responsible for the modest affinities of DPV022 for BH3 domains. These findings reveal that domain-swapped dimeric Bcl-2 folds are not unusual and may be found more widely in viruses. Furthermore, the modest affinities of DPV022 for pro-death Bcl-2 proteins suggest that two distinct classes of anti-apoptotic viral Bcl-2 proteins exist: those that are monomeric and tightly bind a range of death-inducing Bcl-2 proteins, and others such as DPV022 that are dimeric and only bind a very limited number of death-inducing Bcl-2 proteins with modest affinities.

PubMed: 26249341
DOI: 10.1107/S1399004715009402

実験手法

X-RAY DIFFRACTION (3 Å)