5W1X

Crystal Structure of Humanpapillomavirus18 (HPV18) Capsid L1 Pentamers Bound to Heparin Oligosaccharides

Replaces:  3OFL

Summary for 5W1X

• Entry DOI: 10.2210/pdb5w1x/pdb
• Descriptor: Major capsid protein L1, 2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-alpha-D-glucopyranose, 2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-alpha-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: protein oligosaccharide complex, jelly roll, capsid protein, binds to host receptor, receptor heparin oligosaccharides, virus capsid, viral protein
• Biological source: Human papillomavirus type 18; More
• Total number of polymer chains: 15
• Total formula weight: 734418.59

Authors

Chen, X.S.,Dasgupta, J. (deposition date: 2017-06-05, release date: 2018-12-12, Last modification date: 2023-10-04)

Primary citation

Dasgupta, J.,Bienkowska-Haba, M.,Ortega, M.E.,Patel, H.D.,Bodevin, S.,Spillmann, D.,Bishop, B.,Sapp, M.,Chen, X.S.
Structural basis of oligosaccharide receptor recognition by human papillomavirus.
J. Biol. Chem., 286:2617-2624, 2011

PubMed 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.

PubMed: 21115492
DOI: 10.1074/jbc.M110.160184

Experimental method

X-RAY DIFFRACTION (3.374 Å)