5EWN

Crystal structure of the human astrovirus 1 capsid protein core domain at 2.6 A resolution

Summary for 5EWN

• Entry DOI: 10.2210/pdb5ewn/pdb
• Descriptor: Structural protein, CHLORIDE ION (3 entities in total)
• Functional Keywords: virus protein, capsid protein, icosahedral virus, jelly-roll, viral protein
• Biological source: Human astrovirus-1 (HAstV-1)
• Total number of polymer chains: 2
• Total formula weight: 80061.66

Authors

York, R.L.,Yousefi, P.A.,Bogdanoff, W.,Haile, S.,Tripathi, S.,DuBois, R.M. (deposition date: 2015-11-20, release date: 2015-12-23, Last modification date: 2024-11-13)

Primary citation

York, R.L.,Yousefi, P.A.,Bogdanoff, W.,Haile, S.,Tripathi, S.,DuBois, R.M.
Structural, Mechanistic, and Antigenic Characterization of the Human Astrovirus Capsid.
J.Virol., 90:2254-2263, 2015

PubMed Abstract: Human astroviruses (HAstVs) are nonenveloped, positive-sense, single-stranded RNA viruses that are a leading cause of viral gastroenteritis. HAstV particles display T=3 icosahedral symmetry formed by 180 copies of the capsid protein (CP), which undergoes proteolytic maturation to generate infectious HAstV particles. Little is known about the molecular features that govern HAstV particle assembly, maturation, infectivity, and immunogenicity. Here we report the crystal structures of the two main structural domains of the HAstV CP: the core domain at 2.60-Å resolution and the spike domain at 0.95-Å resolution. Fitting of these structures into the previously determined 25-Å-resolution electron cryomicroscopy density maps of HAstV allowed us to characterize the molecular features on the surfaces of immature and mature T=3 HAstV particles. The highly electropositive inner surface of HAstV supports a model in which interaction of the HAstV CP core with viral RNA is a driving force in T=3 HAstV particle formation. Additionally, mapping of conserved residues onto the HAstV CP core and spike domains in the context of the immature and mature HAstV particles revealed dramatic changes to the exposure of conserved residues during virus maturation. Indeed, we show that antibodies raised against mature HAstV have reactivity to both the HAstV CP core and spike domains, revealing for the first time that the CP core domain is antigenic. Together, these data provide new molecular insights into HAstV that have practical applications for the development of vaccines and antiviral therapies.

PubMed: 26656707
DOI: 10.1128/JVI.02666-15

Experimental method

X-RAY DIFFRACTION (2.602 Å)