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Oligomerization of neutral peptides derived from the JC virus agnoprotein through a cysteine residue

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Abstract

The JC virus is the causative agent of progressive multifocal leukoencephalopathy. The viral genome encodes a multifunctional protein known as agnoprotein which is essential for viral proliferation and reported to possess the oligomerization sequence. However, the structural relationship with the oligomerization is unclear. We synthesized 23 amino acid residue neutral peptides derived from the JC virus agnoprotein, Lys22 to Asp44. The secondary structures of these peptides were β-sheet in aqueous buffer that converted to a helical structure in a hydrophobic environment. These peptides interestingly formed dimers and oligomers under oxidizing conditions. The oligomerization was facilitated by addition of bismaleimides and the derivative without thiol group did not form such oligomers. These results suggest that Agno(22–44) could be transmembrane and one disulfide bond between Cys40 triggers the oligomerization.

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Abbreviations

Agno:

Agnoprotein

BMB:

1,4-Bis(maleimido)butane

BME:

1,2-Bis(maleimido)ethane

DTT:

Dithiothreitol

DSS:

Di(N-succinimidyl) suberate

GSSG:

Oxidized glutathione

HOBt:

1-Hydroxybenzotriazole

NEM:

N-ethylmaleimide

PML:

Progressive multifocal leukoencephalopathy

PyBOP:

Benzotriazole-1-yloxy-tripyrrolidinophosphonium hexafluorophosphate

TFE:

2,2,2-Trifluoroethanol

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Acknowledgments

We are sincerely grateful to Dr. M. Otani for technical advice and to Dr. T. Yamashita for graphical advice on the electrophoresis. This research was supported in part by the Strategic Research Foundation at Private Universities from MEXT, Japan.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

The manuscript does not contain clinical studies or patients data.

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe, 650-8586, Japan

    Koushi Hidaka, Keiko Hojo, Shio Fujioka & Yuko Tsuda

  2. Cooperative Research Center for Life Sciences, Kobe Gakuin University, Kobe, 650-8586, Japan

    Koushi Hidaka, Keiko Hojo & Yuko Tsuda

  3. Department of Infectious Diseases, Kobe Institute of Health, Kobe, 650-0046, Japan

    Souichi Nukuzuma

Authors
  1. Koushi Hidaka
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  2. Keiko Hojo
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  3. Shio Fujioka
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  4. Souichi Nukuzuma
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  5. Yuko Tsuda
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Correspondence to Koushi Hidaka.

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Handling Editor: J. Bode.

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Hidaka, K., Hojo, K., Fujioka, S. et al. Oligomerization of neutral peptides derived from the JC virus agnoprotein through a cysteine residue. Amino Acids 47, 2205–2213 (2015). https://doi.org/10.1007/s00726-015-2004-3

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  • DOI: https://doi.org/10.1007/s00726-015-2004-3

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