5KOV

Crystal structure of the human astrovirus 2 capsid protein spike in complex with a single chain variable fragment of an astrovirus neutralizing antibody at 3.24-A resolution

Summary for 5KOV

• Entry DOI: 10.2210/pdb5kov/pdb
• Descriptor: Capsid polyprotein VP90, PL-2 scFv chain, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: viral protein, capsid protein, icosahedral virus, single chain variable fragment.
• Biological source: Human astrovirus-2 (HAstV-2); More
• Total number of polymer chains: 16
• Total formula weight: 422557.46

Authors

Bogdanoff, W.A.,DuBois, R.M. (deposition date: 2016-07-01, release date: 2016-11-09, Last modification date: 2024-10-30)

Primary citation

Bogdanoff, W.A.,Campos, J.,Perez, E.I.,Yin, L.,Alexander, D.L.,DuBois, R.M.
Structure of a Human Astrovirus Capsid-Antibody Complex and Mechanistic Insights into Virus Neutralization.
J. Virol., 91:-, 2017

PubMed Abstract: Human astroviruses (HAstVs) are a leading cause of viral diarrhea in young children, the immunocompromised, and the elderly. There are no vaccines or antiviral therapies against HAstV disease. Several lines of evidence point to the presence of protective antibodies in healthy adults as a mechanism governing protection against reinfection by HAstV. However, development of anti-HAstV therapies is hampered by the gap in knowledge of protective antibody epitopes on the HAstV capsid surface. Here, we report the structure of the HAstV capsid spike domain bound to the neutralizing monoclonal antibody PL-2. The antibody uses all six complementarity-determining regions to bind to a quaternary epitope on each side of the dimeric capsid spike. We provide evidence that the HAstV capsid spike is a receptor-binding domain and that the antibody neutralizes HAstV by blocking virus attachment to cells. We identify patches of conserved amino acids that overlap the antibody epitope and may comprise a receptor-binding site. Our studies provide a foundation for the development of therapies to prevent and treat HAstV diarrheal disease.

PubMed: 27807234
DOI: 10.1128/JVI.01859-16

Experimental method

X-RAY DIFFRACTION (3.245 Å)