2XPX

Crystal structure of BHRF1:Bak BH3 complex

Summary for 2XPX

• Entry DOI: 10.2210/pdb2xpx/pdb
• Related: 1BXL 1Q59 2JBY 2JCN
• Descriptor: APOPTOSIS REGULATOR BHRF1, BCL-2 HOMOLOGOUS ANTAGONIST/KILLER, NITRATE ION, ... (5 entities in total)
• Functional Keywords: apoptosis, membrane protein
• Biological source: HUMAN HERPESVIRUS 4; More
• Cellular location: Host membrane; Single-pass membrane protein (Potential): P03182; Mitochondrion membrane; Single-pass membrane protein (Potential): Q16611
• Total number of polymer chains: 2
• Total formula weight: 23102.67

Authors

Kvansakul, M.,Huang, D.C.S.,Colman, P.M. (deposition date: 2010-08-31, release date: 2011-01-26, Last modification date: 2023-12-20)

Primary citation

Kvansakul, M.,Wei, A.H.,Fletcher, J.I.,Willis, S.N.,Chen, L.,Roberts, A.W.,Huang, D.C.S.,Colman, P.M.
Structural Basis for Apoptosis Inhibition by Epstein-Barr Virus Bhrf1.
Plos Pathog., 6:1236-, 2010

PubMed Abstract: Epstein-Barr virus (EBV) is associated with human malignancies, especially those affecting the B cell compartment such as Burkitt lymphoma. The virally encoded homolog of the mammalian pro-survival protein Bcl-2, BHRF1 contributes to viral infectivity and lymphomagenesis. In addition to the pro-apoptotic BH3-only protein Bim, its key target in lymphoid cells, BHRF1 also binds a selective sub-set of pro-apoptotic proteins (Bid, Puma, Bak) expressed by host cells. A consequence of BHRF1 expression is marked resistance to a range of cytotoxic agents and in particular, we show that its expression renders a mouse model of Burkitt lymphoma untreatable. As current small organic antagonists of Bcl-2 do not target BHRF1, the structures of it in complex with Bim or Bak shown here will be useful to guide efforts to target BHRF1 in EBV-associated malignancies, which are usually associated with poor clinical outcomes.

PubMed: 21203485
DOI: 10.1371/JOURNAL.PPAT.1001236

Experimental method

X-RAY DIFFRACTION (2.05 Å)