2O42

Crystal Structure of M11L, Bcl-2 homolog from myxoma virus

2O42 の概要

• エントリーDOI: 10.2210/pdb2o42/pdb
• 分子名称: M11L protein (2 entities in total)
• 機能のキーワード: apoptosis inhibitor, poxvirus, bcl-2 homolog
• 由来する生物種: Myxoma virus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 33122.45

構造登録者

Douglas, A.E. (登録日: 2006-12-02, 公開日: 2007-03-06, 最終更新日: 2024-10-16)

主引用文献

Douglas, A.E.,Corbett, K.D.,Berger, J.M.,McFadden, G.,Handel, T.M.
Structure of M11L: A myxoma virus structural homolog of the apoptosis inhibitor, Bcl-2.
Protein Sci., 16:695-703, 2007

PubMed Abstract: Apoptosis of virally infected cells is an innate host mechanism used to prevent viral spread. However, viruses have evolved a number of proteins that function to modulate the apoptotic cascades and thereby favor productive viral replication. One such antiapoptotic protein, myxoma virus M11L, has been shown to inhibit mitochondrial-dependent apoptosis by binding to and blocking the two executioner proteins Bak and Bax. Since M11L has no obvious sequence homology with Bcl-2 or Bcl-x(L), the normal cellular inhibitors for Bak and Bax, and the structure of M11L has not been solved, the mode of binding to Bak and Bax is not known. In order to understand how M11L functions, the crystal structure of M11L was solved to 2.91 A. Despite the lack of sequence similarity, M11L is a structural homolog of Bcl-2. Studies using a peptide derived from Bak indicate that M11L binds to Bak with a similar affinity (4.9 +/- 0.3 microM) to the published binding affinities of Bcl-2 and Bcl-x(L) to the same peptide (12.7 microM and 0.5 microM, respectively), indicating that M11L inhibits apoptosis by mimicking and competing with host proteins for the binding of Bak and Bax. The structure provides important insight into how myxoma virus and other poxviruses facilitate viral dissemination by inhibiting mitochondrial dependent apoptosis.

PubMed: 17384234
DOI: 10.1110/ps.062720107

実験手法

X-RAY DIFFRACTION (2.91 Å)