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Journal of Virology, August 2008, p. 8196-8203, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.00509-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Structural Analysis Reveals an Amyloid Form of the Human Papillomavirus Type 16 E1{wedge}E4 Protein and Provides a Molecular Basis for Its Accumulation{triangledown}

Pauline B. McIntosh,1 Stephen R. Martin,2 Deborah J. Jackson,1 Jameela Khan,1 Erin R. Isaacson,1 Lesley Calder,1 Kenneth Raj,1 Heather M. Griffin,1 Qian Wang,1 Peter Laskey,1 John F. Eccleston,2 and John Doorbar1*

Division of Virology,1 Division of Physical Biochemistry, MRC National Institute for Medical Research, London NW7 1AA, United Kingdom2

Received 7 March 2008/ Accepted 3 June 2008

The abundant human papillomavirus (HPV) type 16 E4 protein exists as two distinct structural forms in differentiating epithelial cells. Monomeric full-length 16E1{wedge}E4 contains a limited tertiary fold constrained by the N and C termini. N-terminal deletions facilitate the assembly of E1{wedge}E4 into amyloid-like fibrils, which bind to thioflavin T. The C-terminal region is highly amyloidogenic, and its deletion abolishes amyloid staining and prevents E1{wedge}E4 accumulation. Amyloid-imaging probes can detect 16E1{wedge}E4 in biopsy material, as well as 18E1{wedge}E4 and 33E1{wedge}E4 in monolayer cells, indicating structural conservation. Our results suggest a role for fibril formation in facilitating the accumulation of E1{wedge}E4 during HPV infection.

* Corresponding author. Mailing address: Division of Virology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. Phone: 44 (0)20 8816 2623. Fax: 44 (0)20 8906 4477. E-mail: jdoorba{at}nimr.mrc.ac.uk

{triangledown} Published ahead of print on 18 June 2008.

Journal of Virology, August 2008, p. 8196-8203, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.00509-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wang, Q., Kennedy, A., Das, P., McIntosh, P. B., Howell, S. A., Isaacson, E. R., Hinz, S. A., Davy, C., Doorbar, J. (2009). Phosphorylation of the Human Papillomavirus Type 16 E1^E4 Protein at T57 by ERK Triggers a Structural Change That Enhances Keratin Binding and Protein Stability. J. Virol. 83: 3668-3683 [Abstract] [Full Text]  


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