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HUMAN RHINOVIRUS 16 COAT PROTEIN AT HIGH RESOLUTION
Structural highlights
FunctionPOLG_HRV16 Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The capsid interacts with human ICAM1 to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin- and caveolin-independent endocytosis (By similarity). VP0 precursor is a component of immature procapsids (By similarity). Protein 2A is a cysteine protease that is responsible for the cleavage between the P1 and P2 regions. It cleaves the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA transcription (By similarity). Protein 2B affects membrane integrity and cause an increase in membrane permeability (By similarity). 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 (By similarity). Protein 3C is a 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 co-operatively to the protease (By similarity). RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBACKGROUND: Rhinoviruses belong to the picornavirus family and are small, icosahedral, non-enveloped viruses containing one positive RNA strand. Human rhinovirus 16 (HRV16) belongs to the major receptor group of rhinoviruses, for which the cellular receptor is intercellular adhesion molecule-1 (ICAM-1). In many rhinoviruses, one of the viral coat proteins (VP1) contains a hydrophobic pocket which is occupied by a fatty acid-like molecule, or so-called 'pocket factor'. Antiviral agents have been shown to bind to the hydrophobic pocket in VP1, replacing the pocket factor. The presence of the antiviral compound blocks uncoating of the virus and in some cases inhibits receptor attachment. A refined, high-resolution structure would be expected to provide further information on the nature of the pocket factor and other features previously not clearly identified. RESULTS: The structure of native HRV16 has been refined to a resolution of 2.15 A. The hydrophobic pocket in VP1 is observed in two alternative conformations. In one of these, the pocket is filled by a pocket factor and the protein structure is similar to virus-antiviral compound complexes. In the other conformation, the hydrophobic pocket is collapsed and empty. RNA bases stack against both a tryptophan and a phenylalanine residue on the internal surface of the viral capsid. Site-directed mutagenesis of the tryptophan, which is conserved across the picornaviruses, to nonconservative residues results in non-viable virus. Five symmetry-related N termini of coat protein VP4 form a ten-stranded, antiparallel beta barrel around the base of the icosahedral fivefold axis. The N termini of VP1 are amphipathic alpha helices, which stack on the outside of this beta barrel. The N termini of VP1 and VP4 have not been observed previously in rhinovirus structures. CONCLUSIONS: The observation of a partially occupied hydrophobic pocket in HRV16 forms a missing link between HRV14, which is always observed with no pocket factor in the native form, and rhinovirus 1A and other picornaviruses (e.g. poliovirus, coxsackievirus) which contain pocket factors. The pocket factor molecules probably regulate viral entry, uncoating and assembly. Picornavirus assembly is known to proceed via pentamers, therefore, the interaction of RNA with the conserved tryptophan residues across twofold axes between pentamers may play a role in picornavirus assembly. The positioning of a cation on the icosahedral fivefold axes and the structure of the N termini of VP4 and VP1 around these axes suggest a mechanism for the uncoating of rhinoviruses. The refined structure of human rhinovirus 16 at 2.15 A resolution: implications for the viral life cycle.,Hadfield AT, Lee W, Zhao R, Oliveira MA, Minor I, Rueckert RR, Rossmann MG Structure. 1997 Mar 15;5(3):427-41. PMID:9083115[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences | ||||||||||||||||||||
