Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-019-11173-1
Title: Structural and functional analyses of hepatitis B virus X protein BH3-like domain and Bcl-xL interaction
Authors: Zhang, T.-Y.
Chen, H.-Y. 
Cao, J.-L.
Xiong, H.-L.
Mo, X.-B.
Li, T.-L.
Kang, X.-Z.
Zhao, J.-H.
Yin, B. 
Zhao, X.
Huang, C.-H.
Yuan, Q.
Xue, D.
Xia, N.-S.
Yuan, Y.A. 
Issue Date: 2019
Publisher: Nature Publishing Group
Citation: Zhang, T.-Y., Chen, H.-Y., Cao, J.-L., Xiong, H.-L., Mo, X.-B., Li, T.-L., Kang, X.-Z., Zhao, J.-H., Yin, B., Zhao, X., Huang, C.-H., Yuan, Q., Xue, D., Xia, N.-S., Yuan, Y.A. (2019). Structural and functional analyses of hepatitis B virus X protein BH3-like domain and Bcl-xL interaction. Nature Communications 10 (1) : 3192. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-019-11173-1
Rights: Attribution 4.0 International
Abstract: Hepatitis B virus (HBV) X protein, HBx, interacts with anti-apoptotic Bcl-2 and Bcl-xL proteins through its BH3-like motif to promote HBV replication and cytotoxicity. Here we report the crystal structure of HBx BH3-like motif in complex with Bcl-xL where the BH3-like motif adopts a short ?-helix to snuggle into a hydrophobic pocket in Bcl-xL via its noncanonical Trp120 residue and conserved Leu123 residue. This binding pocket is ~2 Å away from the canonical BH3-only binding pocket in structures of Bcl-xL with proapoptotic BH3-only proteins. Mutations altering Trp120 and Leu123 in HBx impair its binding to Bcl-xL in vitro and HBV replication in vivo, confirming the importance of this motif to HBV. A HBx BH3-like peptide, HBx-aa113-135, restores HBV replication from a HBx-null HBV replicon, while a shorter peptide, HBx-aa118-127, inhibits HBV replication. These results provide crucial structural and functional insights into drug designs for inhibiting HBV replication and treating HBV patients. © 2019, The Author(s).
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/212758
ISSN: 20411723
DOI: 10.1038/s41467-019-11173-1
Rights: Attribution 4.0 International
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