Structural basis of oligosaccharide receptor recognition by human papillomavirus.
J Biol Chem
; 286(4): 2617-24, 2011 Jan 28.
Article
in En
| MEDLINE
| ID: mdl-21115492
ABSTRACT
High risk human papillomavirus types 16 (HPV16) and 18 (HPV18) can cause cervical cancer. Efficient infection by HPV16 and HPV18 pseudovirions requires interactions of particles with cell-surface receptor heparan sulfate oligosaccharide. To understand the virus-receptor interactions for HPV infection, we determined the crystal structures of HPV16 and HPV18 capsids bound to the oligosaccharide receptor fragment using oligomeric heparin. The HPV-heparin structures revealed multiple binding sites for the highly negatively charged oligosaccharide fragment on the capsid surface, which is different from previously reported virus-receptor interactions in which a single type of binding pocket is present for a particular receptor. We performed structure-guided mutagenesis to generate mutant viruses, and cell binding and infectivity assays demonstrated the functional role of viral residues involved in heparin binding. These results provide a basis for understanding virus-heparan sulfate receptor interactions critical for HPV infection and for the potential development of inhibitors against HPV infection.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Human papillomavirus 16
/
Human papillomavirus 18
/
Heparitin Sulfate
Limits:
Humans
Language:
En
Journal:
J Biol Chem
Year:
2011
Document type:
Article
Affiliation country: