8ghs | pdb_00008ghs
Empty HBV Cp183 capsid with importin-beta, subparticle reconstruction at 2-fold location
Structural highlights
FunctionPublication Abstract from PubMedMany viruses undergo transient conformational change to surveil their environments for receptors and host factors. In Hepatitis B Virus (HBV) infection, after the virus enters the cell it is transported to the nucleus by interaction of the HBV capsid with an importin alpha/beta complex. The interaction between the virus and the importins is mediated by nuclear localization signals on the capsid protein C-terminal domain (CTD). However, CTDs are located inside the capsid. In this study we asked: where does a CTD exit the capsid, are all quasi-equivalent CTDs created equal, and does the capsid structure deform to facilitate CTD egress from the capsid? Here, we used Impbeta as a tool to trap transiently exposed CTDs and examined this complex by cryo-electron microscopy. We examined structures in an asymmetric reconstruction of a T=4 icosahedral capsid and a focused reconstruction of a quasi-sixfold vertex (3.8 and 4.0 A resolution, respectively). With both approaches, we observed that a subset of CTDs extended through a pore in the center of the quasi-sixfold complex. CTD egress was accompanied by enlargement of the pore and subtle changes in quaternary and tertiary structure of the quasi-sixfold. When compared to molecular dynamics simulations, structural changes were within the normal range of capsid flexibility. Although pore diameter was enlarged in the Impbeta-bound reconstruction, simulations indicate that CTD egress does not exclusively depend on enlarged pores. In summary, we find that HBV surveillance of its environment by transient exposure of its CTD, requires only modest conformational change of the capsid. Structure of the Hepatitis B Virus capsid quasi-sixfold with a trapped C-terminal domain reveals capsid movements associated with domain exit.,Kim C, Schlicksup CJ, Perez-Segura C, Hadden-Perilla JA, Che-Yen Wang J, Zlotnick A J Biol Chem. 2023 Jul 28:105104. doi: 10.1016/j.jbc.2023.105104. PMID:37517693[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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