4QPG

Crystal structure of empty hepatitis A virus

Summary for 4QPG

• Entry DOI: 10.2210/pdb4qpg/pdb
• Descriptor: Capsid protein VP1, Capsid protein VP0, Capsid protein VP3, ... (5 entities in total)
• Functional Keywords: evolution, insect picorna-like viruses, icosahedral, domain swap, beta-barrel, virus, picornavirus, pathogen, liver
• Biological source: Human hepatitis A virus; More
• Total number of polymer chains: 3
• Total formula weight: 76180.11

Authors

Wang, X.,Ren, J.,Gao, Q.,Hu, Z.,Sun, Y.,Li, X.,Rowlands, D.J.,Yin, W.,Wang, J.,Stuart, D.I.,Rao, Z.,Fry, E.E. (deposition date: 2014-06-23, release date: 2014-10-15, Last modification date: 2023-09-20)

Primary citation

Wang, X.,Ren, J.,Gao, Q.,Hu, Z.,Sun, Y.,Li, X.,Rowlands, D.J.,Yin, W.,Wang, J.,Stuart, D.I.,Rao, Z.,Fry, E.E.
Hepatitis A virus and the origins of picornaviruses.
Nature, 517:85-88, 2015

PubMed Abstract: Hepatitis A virus (HAV) remains enigmatic, despite 1.4 million cases worldwide annually. It differs radically from other picornaviruses, existing in an enveloped form and being unusually stable, both genetically and physically, but has proved difficult to study. Here we report high-resolution X-ray structures for the mature virus and the empty particle. The structures of the two particles are indistinguishable, apart from some disorder on the inside of the empty particle. The full virus contains the small viral protein VP4, whereas the empty particle harbours only the uncleaved precursor, VP0. The smooth particle surface is devoid of depressions that might correspond to receptor-binding sites. Peptide scanning data extend the previously reported VP3 antigenic site, while structure-based predictions suggest further epitopes. HAV contains no pocket factor and can withstand remarkably high temperature and low pH, and empty particles are even more robust than full particles. The virus probably uncoats via a novel mechanism, being assembled differently to other picornaviruses. It utilizes a VP2 'domain swap' characteristic of insect picorna-like viruses, and structure-based phylogenetic analysis places HAV between typical picornaviruses and the insect viruses. The enigmatic properties of HAV may reflect its position as a link between 'modern' picornaviruses and the more 'primitive' precursor insect viruses; for instance, HAV retains the ability to move from cell-to-cell by transcytosis.

PubMed: 25327248
DOI: 10.1038/nature13806

Experimental method

X-RAY DIFFRACTION (3.5 Å)