Structural analysis reveals an amyloid form of the human papillomavirus type 16 E1--E4 protein and provides a molecular basis for its accumulation.
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.
Division of Virology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom.
Pauline B
PB
McIntosh
Stephen R
SR
Martin
Deborah J
DJ
Jackson
Jameela
J
Khan
Erin R
ER
Isaacson
Lesley
L
Calder
Kenneth
K
Raj
Heather M
HM
Griffin
Qian
Q
Wang
Peter
P
Laskey
John F
JF
Eccleston
John
J
Doorbar
D000595:Amino Acid Sequence; D000818:Animals; D001706:Biopsy; D019556:COS Cells; D002522:Chlorocebus aethiops; D017353:Gene Deletion; D052162:Human papillomavirus 16 / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid