Calcium bridge triggers capsid disassembly in the cell entry process of simian virus 40

Masa Aki Kawano, Li Xing, Hiroto Tsukamoto, Takamasa Inoue, Hiroshi Handa, R. Holland Cheng

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

The calcium bridge between the pentamers of polyoma viruses maintains capsid metastability. It has been shown that viral infection is profoundly inhibited by the substitution of lysine for glutamate in one calcium-binding residue of the SV40 capsid protein, VP1. However, it is unclear how the calcium bridge affects SV40 infectivity. In this in vitro study, we analyzed the influence of host cell components on SV40 capsid stability. We used an SV40 mutant capsid (E330K) in which lysine had been substituted for glutamate 330 in protein VP1. The mutant capsid retained the ability to interact with the SV40 cellular receptor GM1, and the internalized mutant capsid accumulated in caveolin-1-mediated endocytic vesicles and was then translocated to the endoplasmic reticulum (ER) region. However, when placed in ER-rich microsome, the mutant capsid retained its spherical structure in contrast to the wild type, which disassembled. Structural analysis of the mutant capsid with cryo-electron microscopy and image reconstruction revealed altered pentamer coordination, possibly as a result of electrostatic interaction, although its overall structure resembled that of the wild type. These results indicate that the calcium ion serves as a trigger at the pentamer interface, which switches on capsid disassembly, and that the failure of the E330K mutant capsid to disassemble is attributable to an inadequate triggering system. Our data also indicate that calcium depletion-induced SV40 capsid disassembly may occur in the ER region and that this is essential for successful SV40 infection.

Original languageEnglish (US)
Pages (from-to)34703-34712
Number of pages10
JournalJournal of Biological Chemistry
Volume284
Issue number50
DOIs
StatePublished - Dec 11 2009

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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    Kawano, M. A., Xing, L., Tsukamoto, H., Inoue, T., Handa, H., & Cheng, R. H. (2009). Calcium bridge triggers capsid disassembly in the cell entry process of simian virus 40. Journal of Biological Chemistry, 284(50), 34703-34712. https://doi.org/10.1074/jbc.M109.015107