1dgi
From Proteopedia
Cryo-EM structure of human poliovirus(serotype 1)complexed with three domain CD155
Structural highlights
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.[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] [PVR_HUMAN] Mediates NK cell adhesion and triggers NK cell effector functions. Binds two different NK cell receptors: CD96 and CD226. These interactions accumulates at the cell-cell contact site, leading to the formation of a mature immunological synapse between NK cell and target cell. This may trigger adhesion and secretion of lytic granules and IFN-gamma and activate cytoxicity of activated NK cells. May also promote NK cell-target cell modular exchange, and PVR transfer to the NK cell. This transfer is more important in some tumor cells expressing a lot of PVR, and may trigger fratricide NK cell activation, providing tumors with a mechanism of immunoevasion. Plays a role in mediating tumor cell invasion and migration. Serves as a receptor for poliovirus attachment to target cells. May play a role in axonal transport of poliovirus, by targeting virion-PVR-containing endocytic vesicles to the microtubular network through interaction with DYNLT1. This interaction would drive the virus-containing vesicle to the axonal retrograde transport.[25] [26] Evolutionary Conservation Checkto colour the structure by Evolutionary Conservation, 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 the extracellular, three-domain poliovirus receptor (CD155) complexed with poliovirus (serotype 1) has been determined to 22-A resolution by means of cryo-electron microscopy and three-dimensional image-reconstruction techniques. Density corresponding to the receptor was isolated in a difference electron density map and fitted with known structures, homologous to those of the three individual CD155 Ig-like domains. The fit was confirmed by the location of carbohydrate moieties in the CD155 glycoprotein, the conserved properties of elbow angles in the structures of cell surface molecules with Ig-like folds, and the concordance with prior results of CD155 and poliovirus mutagenesis. CD155 binds in the poliovirus "canyon" and has a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. However, the orientation of the long, slender CD155 molecule relative to the poliovirus surface is quite different from the orientation of intercellular adhesion molecule-1 on rhinoviruses. In addition, the residues that provide specificity of recognition differ for the two receptors. The principal feature of receptor binding common to these two picornaviruses is the site in the canyon at which binding occurs. This site may be a trigger for initiation of the subsequent uncoating step required for viral infection. Interaction of the poliovirus receptor with poliovirus.,He Y, Bowman VD, Mueller S, Bator CM, Bella J, Peng X, Baker TS, Wimmer E, Kuhn RJ, Rossmann MG Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):79-84. PMID:10618374[27] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Hpv-1 | Human | Large Structures | Poliovirus and Rhinovirus | RCSB PDB Molecule of the Month | Baker, T S | Bator, C M | Bella, J | Bowman, V D | He, Y | Kuhn, R J | Mueller, S | Peng, X | Rossmann, M G | Wimmer, E | Cd155 | Human poliovirus | Icosahedral virus | Poliovirus-receptor complex | Pvr | Virus-receptor complex
