5FCG

Crystal structure of Bcl-2 in complex with HBx-BH3 motif

Summary for 5FCG

• Entry DOI: 10.2210/pdb5fcg/pdb
• Descriptor: Apoptosis regulator Bcl-2, Protein X (3 entities in total)
• Functional Keywords: complex, apoptosis
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 22603.28

Authors

Jiang, T.Y.,Liu, M.H.,Wu, J.P.,Shi, Y.G. (deposition date: 2015-12-15, release date: 2016-02-10, Last modification date: 2023-11-08)

Primary citation

Jiang, T.Y.,Liu, M.H.,Wu, J.P.,Shi, Y.G.
Structural and biochemical analysis of Bcl-2 interaction with the hepatitis B virus protein HBx
Proc.Natl.Acad.Sci.USA, 2016

PubMed Abstract: HBx is a hepatitis B virus protein that is required for viral infectivity and replication. Anti-apoptotic Bcl-2 family members are thought to be among the important host targets of HBx. However, the structure and function of HBx are poorly understood and the molecular mechanism of HBx-induced carcinogenesis remains unknown. In this study, we report biochemical and structural characterization of HBx. The recombinant HBx protein contains metal ions, in particular iron and zinc. A BH3-like motif in HBx (residues 110-135) binds Bcl-2 with a dissociation constant of ∼193 μM, which is drastically lower than that for a canonical BH3 motif from Bim or Bad. Structural analysis reveals that, similar to other BH3 motifs, the BH3-like motif of HBx adopts an amphipathic α-helix and binds the conserved BH3-binding groove on Bcl-2. Unlike the helical Bim or Bad BH3 motif, the C-terminal portion of the bound HBx BH3-like motif has an extended conformation and makes considerably fewer interactions with Bcl-2. These observations suggest that HBx may modulate Bcl-2 function in a way that is different from that of the classical BH3-only proteins.

PubMed: 26858413
DOI: 10.1073/pnas.1525616113

Experimental method

X-RAY DIFFRACTION (2.1 Å)