1ng7

The Solution Structure of the Soluble Domain of Poliovirus 3A Protein

spinqualitylabelsall models 1ng7 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1ng7 is a 2 chain structure with sequence from Human poliovirus 1. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function POLG_POL1M 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 interaction of five VP1 proteins in the fivefold axes results in a prominent protusion extending to about 25 Angstroms from the capsid shell. The resulting structure appears as a steep plateau encircled by a valley or cleft. This depression also termed canyon is the receptor binding site. The capsid interacts with human PVR at this site to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin- and caveolin-independent endocytosis in Hela cells and through caveolin-mediated endocytosis in brain microvascular endothelial cells. VP4 and VP1 subsequently undergo conformational changes leading to the formation of a pore in the endosomal membrane, thereby delivering the viral genome into the cytoplasm. 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. 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. Protein 3A, via its hydrophobic domain, serves as membrane anchor. It also inhibits endoplasmic reticulum-to-Golgi transport (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 PubMed Poliovirus is a positive-strand RNA virus and the prototypical member of the Picornaviridae family. Upon infection, the viral RNA genome is translated from a single open reading frame into a polypeptide which undergoes a series of cleavages to ultimately form four structural and seven non-structural proteins. A replication complex is then formed which replicates the viral genome into negative and positive strands for further translation, replication, and packaging into viral progeny. Poliovirus 3A protein (3A) is a critical component of the viral replication complex and is the putative target of enviroxime, an antiviral drug shown to block viral replication. 3A also inhibits host cell endoplasmic reticulum-to-Golgi apparatus transport, a function which may play a key role in viral evasion from the host immune response. 3A, an 87-residue protein consisting of a soluble N terminus and a hydrophobic C terminus, is formed by the cleavage of the precursor protein 3AB into 3A and 3B (VPg). Although they differ by only 22 residues, the precursor protein 3AB and its cleavage product 3A have distinct functions in viral replication. We have determined the structure of the soluble, N-terminal domain of 3A (3A-N) using NMR spectroscopy. We show that 3A-N exists as a symmetric dimer, and each monomer consists of an alpha-helical hairpin with unstructured, yet functional, N- and C termini. We also show that the 3A-N structure contains a negatively charged surface patch and provides a context for interpreting the biochemical characteristics of a number of previously reported 3A and 3AB mutants. Towards an understanding of the poliovirus replication complex: the solution structure of the soluble domain of the poliovirus 3A protein.,Strauss DM, Glustrom LW, Wuttke DS J Mol Biol. 2003 Jul 4;330(2):225-34. PMID:12823963 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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