1r1a
CRYSTAL STRUCTURE OF HUMAN RHINOVIRUS SEROTYPE 1A (HRV1A)
Structural highlights
FunctionPOLG_HRV1A Protein VP1: Forms, together with VP2 and VP3, an icosahedral capsid (pseudo T=3), 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome. Protein VP1 mainly forms the vertices of the capsid. VP1 interacts with host cell receptor VLDLR to provide virion attachment to target cell. This attachment induces virion internalization through a cell-type specific entry mechanism. After binding to its receptor, the capsid undergoes conformational changes. VP1 N-terminus (that contains an amphipathic alpha-helix) is externalized, VP4 is released and together, they shape a virion-cell connecting channel and a pore in the host membrane through which RNase-protected transfer of the viral genome takes place. After genome has been released, the channel shrinks (By similarity). Protein VP2: Forms, together with VP1 and VP3, an icosahedral capsid (pseudo T=3), 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). Protein VP3: Forms, together with VP1 and VP2, an icosahedral capsid (pseudo T=3), 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). Protein VP4: Lies on the inner surface of the capsid shell. After binding to the host receptor, the capsid undergoes conformational changes. VP4 is released, VP1 N-terminus is externalized, and together, they shape a virion-cell connecting channel and a pore in the host membrane through which RNase-protected transfer of the viral genome takes place. After genome has been released, the channel shrinks (By similarity). Protein VP0: Protein VP0: VP0 precursor is a component of immature procapsids, which gives rise to VP4 and VP2 after maturation. Allows the capsid to remain inactive before the maturation step (By similarity). Protease 2A: cysteine protease that is responsible for the cleavage between the P1 and P2 regions. It cleaves the host translation initiation factors EIF4G1, in order to shut off the capped cellular mRNA transcription. Protease 2A also degrades host nucleoporins NUP62, NUP98 and NUP153 thereby blocking the nucleo-cytoplasmic trafficking, in particular the export of cellular mRNAs. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response (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: 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. Cleaves Nup153, Nup214, and Nup358 thereby blocking the nucleo-cytoplasmic trafficking. Contributes to host cell shutoff in infected cells by localizing in the nucleus and facilitating nuclear pore breakdown (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 PubMedThe structure of human rhinovirus 1A (HRV1A) has been determined to 3.2 A resolution using phase refinement and extension by symmetry averaging starting with phases at 5 A resolution calculated from the known human rhinovirus 14 (HRV14) structure. The polypeptide backbone structures of HRV1A and HRV14 are similar, but the exposed surfaces are rather different. Differential charge distribution of amino acid residues in the "canyon", the putative receptor binding site, provides a possible explanation for the difference in minor versus major receptor group specificities, represented by HRV1A and HRV14, respectively. The hydrophobic pocket in VP1, into which antiviral compounds bind, is in an "open" conformation similar to that observed in drug-bound HRV14. Drug binding in HRV1A does not induce extensive conformational changes, in contrast to the case of HRV14. Crystal structure of human rhinovirus serotype 1A (HRV1A).,Kim SS, Smith TJ, Chapman MS, Rossmann MC, Pevear DC, Dutko FJ, Felock PJ, Diana GD, McKinlay MA J Mol Biol. 1989 Nov 5;210(1):91-111. PMID:2555523[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences | ||||||||||||||||||||
