4z92
From Proteopedia
crystal structure of parechovirus-1 virion
Structural highlights
FunctionPOLG_HPE1H Capsid proteins VP0, VP2, VP3 form a closed capsid enclosing the viral positive strand RNA genome. Capsid proteins interact with host alpha-V/beta-3 integrin heterodimer to provide virion attachment target cell. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis.[1] Protein 2A: Is not a protease. Protein 2B: Affects membrane integrity and cause an increase in membrane permeability. Protein 2C: Associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity). Protein 3A, via its hydrophobic domain, serves as membrane anchor. Protease 3C: cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind cooperatively to the protease (By similarity). RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals.[PROSITE-ProRule:PRU00539] Publication Abstract from PubMedParechoviruses are human pathogens that cause diseases ranging from gastrointestinal disorders to encephalitis. Unlike most picornaviruses, parechovirus capsids are composed of only three subunits: VP0, VP1, and VP3. Here we present the structure of a human parechovirus-1 (HPeV-1) virion determined to a resolution of 3.1 A. We find that interactions among pentamers in the HPeV-1 capsid are mediated by the N-termini of VP0s, which correspond to the capsid protein VP4 and the N-terminal part of the capsid protein VP2 of other picornaviruses. In order to facilitate delivery of the virus genome into the cytoplasm, the N-termini of VP0s have to be released from contacts between pentamers and exposed at the particle surface, resulting in capsid disruption. A hydrophobic pocket, which can be targeted by capsid-binding anti-viral compounds in many other picornaviruses, is not present in HPeV-1. However, we found that interactions between the HPeV-1 ssRNA genome and subunits VP1 and VP3 in the virion impose a partial icosahedral ordering on the genome. The residues involved in the RNA binding are conserved among all parechoviruses, suggesting putative role of the genome in virion stability or assembly. Therefore, putative small molecules that could disrupt HPeV RNA-capsid protein interactions could be developed into antiviral inhibitors. IMPORTANCE: Human Parechoviruses (HPeV) are pathogens that cause diseases ranging from respiratory and gastrointestinal disorders to encephalitis. Recently, there have been outbreaks of HPeV infections in Western Europe and North America. We present the first atomic structure of parechovirus HPeV-1 determined by X-ray crystallography. The structure explains why HPeVs cannot be targeted by anti-viral compounds that are effective against other picornaviruses. Furthermore, we found that the interactions of the HPeV-1 genome with the capsid resulted in a partially icosahedral ordering of the genome. The residues involved in the RNA binding are conserved among all parechoviruses, suggesting an evolutionarily fixed role of the genome in virion assembly. Therefore, putative small molecules disrupting HPeV RNA-capsid protein interactions could be developed into antiviral inhibitors. The structure of Human Parechovirus-1 reveals an association of the RNA genome with the capsid.,Kalynych S, Palkova L, Plevka P J Virol. 2015 Nov 18. pii: JVI.02346-15. PMID:26581987[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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