5kov
From Proteopedia
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
Structural highlights
Function[CAPSD_HASV2] The capsid polyprotein VP90 self-assembles and undergoes a proteolytic cleavage by host caspases to yield the VP70 virions. This immature virion is composed of 180 VP70 subunits with 90 dimeric spikes and displays a T=3 icosahedral symmetry. The mature virion is obtained by further cleavages resulting in three structural proteins VP25, VP27 and VP34. This forms contains only 30 spikes located on the icosahedral 2-fold axes. Plays a role in the attachment to target host cell. This attachment induces virion internalization through clathrin-dependent endocytosis (By similarity). Publication Abstract from PubMedHuman astroviruses (HAstVs) are a leading cause of viral diarrhea in young children, the immune compromised, 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 with 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. IMPORTANCE: Human astroviruses (HAstVs) infect nearly every person in the world during childhood and cause diarrhea, vomiting, and fever. Despite the prevalence of this virus, little is known about how antibodies in healthy adults protect them against reinfection. Here, we determined the crystal structure of a complex of the HAstV capsid protein and a virus-neutralizing antibody. We show that the antibody binds to the outermost spike domain of the capsid, and we provide evidence that the antibody blocks virus attachment to human cells. Importantly, our findings suggest that a subunit-based vaccine focusing the immune system on the HAstV capsid spike domain could be effective in protecting children against HAstV disease. Structure of a Human Astrovirus Capsid - Antibody Complex and Mechanistic Insights into Virus Neutralization.,Bogdanoff WA, Campos J, Perez EI, Yin L, Alexander DL, DuBois RM J Virol. 2016 Nov 2. pii: JVI.01859-16. PMID:27807234[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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