Structural Analysis Reveals an Amyloid Form of the Human Papillomavirus Type 16 E1 ∧ E4 Protein and Provides a Molecular Basis for Its Accumulation
- 15 August 2008
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 82 (16), 8196-8203
- https://doi.org/10.1128/jvi.00509-08
Abstract
The abundant human papillomavirus (HPV) type 16 E4 protein exists as two distinct structural forms in differentiating epithelial cells. Monomeric full-length 16E1 ∧ E4 contains a limited tertiary fold constrained by the N and C termini. N-terminal deletions facilitate the assembly of E1 ∧ 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 ∧ E4 accumulation. Amyloid-imaging probes can detect 16E1 ∧ E4 in biopsy material, as well as 18E1 ∧ E4 and 33E1 ∧ E4 in monolayer cells, indicating structural conservation. Our results suggest a role for fibril formation in facilitating the accumulation of E1 ∧ E4 during HPV infection.Keywords
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