4D5T

Structure of N-terminally truncated A49 from Vaccinia Virus Western Reserve

4D5T の概要

• エントリーDOI: 10.2210/pdb4d5t/pdb
• 関連するPDBエントリー: 4D5R 4D5S
• 分子名称: PROTEIN A49R, SULFATE ION (3 entities in total)
• 機能のキーワード: viral protein, pox virus, b cell lymphoma 2 (bcl-2) family, innate immune modulator, nuclear factor kappa b (nf-kb)
• 由来する生物種: VACCINIA VIRUS
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 149601.60

構造登録者

Neidel, S.,Maluquer de Motes, C.,Mansur, D.S.,Strnadova, P.,Smith, G.L.,Graham, S.C. (登録日: 2014-11-07, 公開日: 2015-01-21, 最終更新日: 2023-12-20)

主引用文献

Neidel, S.,Maluquer De Motes, C.,Mansur, D.S.,Strnadova, P.,Smith, G.L.,Graham, S.C.
Vaccinia Virus Protein A49 is an Unexpected Member of the B-Cell Lymphoma (Bcl)-2 Protein Family
J.Biol.Chem., 290:5991-, 2015

PubMed Abstract: Vaccinia virus (VACV) encodes several proteins that inhibit activation of the proinflammatory transcription factor nuclear factor κB (NF-κB). VACV protein A49 prevents translocation of NF-κB to the nucleus by sequestering cellular β-TrCP, a protein required for the degradation of the inhibitor of κB. A49 does not share overall sequence similarity with any protein of known structure or function. We solved the crystal structure of A49 from VACV Western Reserve to 1.8 Å resolution and showed, surprisingly, that A49 has the same three-dimensional fold as Bcl-2 family proteins despite lacking identifiable sequence similarity. Whereas Bcl-2 family members characteristically modulate cellular apoptosis, A49 lacks a surface groove suitable for binding BH3 peptides and does not bind proapoptotic Bcl-2 family proteins Bax or Bak. The N-terminal 17 residues of A49 do not adopt a single well ordered conformation, consistent with their proposed role in binding β-TrCP. Whereas pairs of A49 molecules interact symmetrically via a large hydrophobic surface in crystallo, A49 does not dimerize in solution or in cells, and we propose that this hydrophobic interaction surface may mediate binding to a yet undefined cellular partner. A49 represents the eleventh VACV Bcl-2 family protein and, despite these proteins sharing very low sequence identity, structure-based phylogenetic analysis shows that all poxvirus Bcl-2 proteins are structurally more similar to each other than they are to any cellular or herpesvirus Bcl-2 proteins. This is consistent with duplication and diversification of a single BCL2 family gene acquired by an ancestral poxvirus.

PubMed: 25605733
DOI: 10.1074/JBC.M114.624650

実験手法

X-RAY DIFFRACTION (1.84 Å)