2ABO

NMR structure of gamma herpesvirus 68 a viral Bcl-2 homolog

2ABO の概要

• エントリーDOI: 10.2210/pdb2abo/pdb
• 分子名称: bcl-2 homolog (1 entity in total)
• 機能のキーワード: viral bcl-2 homolog, murine gamma herpes virus, viral protein
• 由来する生物種: Murid herpesvirus 4 (Murine herpesvirus 68)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15752.92

構造登録者

Loh, J.,Huang, Q.,Petros, A.M.,Nettesheim, D.,van Dyk, L.F.,Labrada, L.,Speck, S.H.,Levine, B.,Olejniczak, E.T.,Virgin, H.W. (登録日: 2005-07-15, 公開日: 2006-05-16, 最終更新日: 2024-05-22)

主引用文献

Loh, J.,Huang, Q.,Petros, A.M.,Nettesheim, D.,van Dyk, L.F.,Labrada, L.,Speck, S.H.,Levine, B.,Olejniczak, E.T.,Virgin, H.W.
A surface groove essential for viral Bcl-2 function during chronic infection in vivo.
Plos Pathog., 1:e10-e10, 2005

PubMed Abstract: Antiapoptotic Bcl-2 family proteins inhibit apoptosis in cultured cells by binding BH3 domains of proapoptotic Bcl-2 family members via a hydrophobic BH3 binding groove on the protein surface. We investigated the physiological importance of the BH3 binding groove of an antiapoptotic Bcl-2 protein in mammals in vivo by analyzing a viral Bcl-2 family protein. We show that the gamma-herpesvirus 68 (gammaHV68) Bcl-2 family protein (gammaHV68 v-Bcl-2), which is known to inhibit apoptosis in cultured cells, inhibits both apoptosis in primary lymphocytes and Bax toxicity in yeast. Nuclear magnetic resonance determination of the gammaHV68 v-Bcl-2 structure revealed a BH3 binding groove that binds BH3 domain peptides from proapoptotic Bcl-2 family members Bax and Bak via a molecular mechanism shared with host Bcl-2 family proteins, involving a conserved arginine in the BH3 peptide binding groove. Mutations of this conserved arginine and two adjacent amino acids to alanine (SGR to AAA) within the BH3 binding groove resulted in a properly folded protein that lacked the capacity of the wild-type gammaHV68 v-Bcl-2 to bind Bax BH3 peptide and to block Bax toxicity in yeast. We tested the physiological importance of this v-Bcl-2 domain during viral infection by engineering viral mutants encoding a v-Bcl-2 containing the SGR to AAA mutation. This mutation resulted in a virus defective for both efficient reactivation of gammaHV68 from latency and efficient persistent gammaHV68 replication. These studies demonstrate an essential functional role for amino acids in the BH3 peptide binding groove of a viral Bcl-2 family member during chronic infection.

PubMed: 16201011
DOI: 10.1371/journal.ppat.0010010

実験手法

SOLUTION NMR