5ku0

expanded poliovirus in complex with VHH 17Bexpanded poliovirus in complex with VHH 17B

5ku0, resolution 4.20Å Show:Asymmetric Unit Biological Assembly Structural highlights 5ku0 is a 4 chain structure with sequence from Camelus dromedarius and Human poliovirus 1 Mahoney. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.2Å Experimental data: Check 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). Publication Abstract from PubMed Using cryoelectron microscopy, expanded 80S-like poliovirions were visualized in complexes with four 80S-specific camelid VHHs (Nanobodies(R)). In all four complexes, the VHHs bind to a site on the top surface of capsid protein VP3, which is hidden in native virus. Interestingly, although the four VHHs bind to the same site, the structures of the expanded virus differ in detail in each complex, suggesting that each of the nanobodies has sampled a range of low energy structures available to the expanded virion. By stabilizing unique structures of expanded virions, VHH binding has permitted a more detailed view of the virus structure than previously was possible, leading to a better understanding of the expansion process that is a critical step in infection. It is now clear which polypeptide chains become disordered, and which become rearranged. The higher resolution of these structures has also revealed well-ordered conformations for the EF loop of VP2, the GH loop of VP3, and the N-terminal extensions of VP1 and VP2, that in retrospect were present in lower-resolution structures but not recognized. These structural observations help to explain pre-existing mutational data, and provide insights into several other stages of the poliovirus life cycle, including the mechanism of receptor-triggered virus expansion. IMPORTANCE: When poliovirus infects a cell, it undergoes a change in its structure in order to pass RNA through its protein coat, but this altered state is short-lived and thus poorly understood. The structures of poliovirus bound to single-domain antibodies presented here capture the altered virus in what appear to be intermediate states. A careful analysis of these structures lets us better understand the molecular mechanism of infection, and how these changes in the virus lead to productive infection events. CryoEM structures of expanded poliovirus with VHHs sample the conformational repertoire of the expanded state.,Strauss M, Schotte L, Karunatilaka KS, Filman DJ, Hogle JM J Virol. 2016 Nov 16. pii: JVI.01443-16. PMID:27852863 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Virus coat proteins 3D structures