1po1
From Proteopedia
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/po/1po1_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/po/1po1_consurf.spt"</scriptWhenChecked> | ||
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/ | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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Current revision
POLIOVIRUS (TYPE 1, MAHONEY) IN COMPLEX WITH R80633, AN INHIBITOR OF VIRAL REPLICATION
Structural highlights
FunctionPOLG_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.[1] [2] [3] VP0 precursor is a component of immature procapsids (By similarity).[4] [5] [6] 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.[7] [8] [9] Protein 2B affects membrane integrity and cause an increase in membrane permeability (By similarity).[10] [11] [12] Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities.[13] [14] [15] Protein 3A, via its hydrophobic domain, serves as membrane anchor. It also inhibits endoplasmic reticulum-to-Golgi transport (By similarity).[16] [17] [18] 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).[19] [20] [21] RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).[22] [23] [24] 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 PubMedCrystal structures of the Mahoney strain of type 1 poliovirus complexed with the antiviral compounds R80633 and R77975 were determined at 2.9 A resolution. These compounds block infection by preventing conformational changes required for viral uncoating. In various drug-poliovirus complexes reported earlier, no significant conformational changes were found in the structures of the capsid proteins. In the structures reported here, the strain of virus is relatively insensitive to these antivirals. Correspondingly, significant conformational changes are necessary to accommodate the drug. These conformational changes affect both the immediate vicinity of the drug binding site, and more distant loops located near the fivefold axis. In addition, small but concerted shifts of the centers of mass of the major capsid proteins consistently have been detected whose magnitudes are correlated inversely with the effectiveness of the drugs. Collectively, the drug complexes appear to sample the conformational repertoire of poliovirus near equilibrium, and thus provide a possible model for the earliest stages of viral uncoating during infection. Ligand-induced conformational changes in poliovirus-antiviral drug complexes.,Hiremath CN, Filman DJ, Grant RA, Hogle JM Acta Crystallogr D Biol Crystallogr. 1997 Sep 1;53(Pt 5):558-70. PMID:15299887[25] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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