2WH6

Crystal structure of anti-apoptotic BHRF1 in complex with the Bim BH3 domain

Summary for 2WH6

• Entry DOI: 10.2210/pdb2wh6/pdb
• Related: 1Q59 2V6Q 2VM6
• Descriptor: EARLY ANTIGEN PROTEIN R, BCL-2-LIKE PROTEIN 11, BROMIDE ION, ... (5 entities in total)
• Functional Keywords: mitochondrion, early protein, transmembrane, viral protein, apoptosis
• Biological source: Epstein-barr virus strain ag876; More
• Cellular location: Host membrane ; Single-pass membrane protein : P03182; Endomembrane system ; Peripheral membrane protein . Isoform BimEL: Mitochondrion. Isoform BimL: Mitochondrion. Isoform BimS: Mitochondrion. Isoform Bim-alpha1: Mitochondrion: O43521
• Total number of polymer chains: 2
• Total formula weight: 24026.38

Authors

Kvansakul, M.,Huang, D.C.S.,Colman, P.M. (deposition date: 2009-05-01, release date: 2010-05-26, Last modification date: 2023-12-13)

Primary citation

Kvansakul, M.,Wei, A.H.,Fletcher, J.I.,Willis, S.N.,Chen, L.,Roberts, A.W.,Huang, D.C.,Colman, P.M.
Structural basis for apoptosis inhibition by Epstein-Barr virus BHRF1.
PLoS Pathog., 6:e1001236-e1001236, 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 (1.5 Å)