8hi2
Structure of EV71 VLP frozen at -183 degree embedded in crystalline ice
Structural highlights
FunctionPOLG_HE71 Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). Capsid protein VP1 mainly forms the vertices of the capsid (By similarity). Capsid protein VP1, together with VP2, interacts with host cell receptor SCARB2 to provide virion attachment to target host cells (By similarity). This attachment induces virion internalization. This attachment induces virion internalization (By similarity). After binding to its receptor, the capsid undergoes conformational changes (By similarity). Capsid protein VP1 N-terminus (that contains an amphipathic alpha-helix) and capsid protein VP4 are externalized (By similarity). Together, they shape a pore in the host membrane through which viral genome is translocated to host cell cytoplasm (By similarity).[UniProtKB:P03300][UniProtKB:Q66479] Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). Capsid protein VP2, together with VP1, interacts with host cell receptor SCARB2 to provide virion attachment to target host cells (By similarity).[UniProtKB:P03300][UniProtKB:Q66479] Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity).[UniProtKB:P03300] Lies on the inner surface of the capsid shell (By similarity). After binding to the host receptor, the capsid undergoes conformational changes (By similarity). Capsid protein VP4 is released, Capsid protein VP1 N-terminus is externalized, and together, they shape a pore in the host membrane through which the viral genome is translocated into the host cell cytoplasm (By similarity).[UniProtKB:P03300] Component of immature procapsids, which is cleaved into capsid proteins VP4 and VP2 after maturation (By similarity). Allows the capsid to remain inactive before the maturation step (By similarity).[UniProtKB:P03300] Cysteine protease that cleaves viral polyprotein and specific host proteins (By similarity). It is responsible for the autocatalytic cleavage between the P1 and P2 regions, which is the first cleavage occurring in the polyprotein (By similarity). Cleaves also the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA translation (By similarity). Inhibits the host nucleus-cytoplasm protein and RNA trafficking by cleaving host members of the nuclear pores (By similarity). Counteracts stress granule formation probably by antagonizing its assembly or promoting its dissassembly (By similarity). Cleaves and inhibits host IFIH1/MDA5, thereby inhibiting the type-I IFN production and the establishment of the antiviral state (By similarity). Cleaves and inhibits host MAVS, thereby inhibiting the type-I IFN production and the establishment of the antiviral state (By similarity).[UniProtKB:P03300][UniProtKB:Q66478] Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca2+ in the cytoplasm of infected cell (By similarity). In turn, high levels of cytoplasmic calcium may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (By similarity). Activates also the mitochondrial apoptotic pathway by activating host BAX (By similarity).[UniProtKB:P03300][UniProtKB:Q66478] Induces and associates with structural rearrangements of intracellular membranes. Displays RNA-binding, nucleotide binding and NTPase activities. May play a role in virion morphogenesis and viral RNA encapsidation by interacting with the capsid protein VP3.[UniProtKB:P03300] Localizes the viral replication complex to the surface of membranous vesicles. Together with protein 3CD binds the Cis-Active RNA Element (CRE) which is involved in RNA synthesis initiation. Acts as a cofactor to stimulate the activity of 3D polymerase, maybe through a nucleid acid chaperone activity.[UniProtKB:P03300] Localizes the viral replication complex to the surface of membranous vesicles (By similarity). It inhibits host cell endoplasmic reticulum-to-Golgi apparatus transport and causes the disassembly of the Golgi complex, possibly through GBF1 interaction (By similarity). This would result in depletion of MHC, trail receptors and IFN receptors at the host cell surface (By similarity). Plays an essential role in viral RNA replication by recruiting ACBD3 and PI4KB at the viral replication sites, thereby allowing the formation of the rearranged membranous structures where viral replication takes place (By similarity).[UniProtKB:P03300] Acts as a primer for viral RNA replication and remains covalently bound to viral genomic RNA. VPg is uridylylated prior to priming replication into VPg-pUpU (By similarity). The oriI viral genomic sequence may act as a template for this. The VPg-pUpU is then used as primer on the genomic RNA poly(A) by the RNA-dependent RNA polymerase to replicate the viral genome (By similarity). Following genome release from the infecting virion in the cytoplasm, the VPg-RNA linkage is probably removed by host TDP2 (By similarity). During the late stage of the replication cycle, host TDP2 is excluded from sites of viral RNA synthesis and encapsidation, allowing for the generation of progeny virions (By similarity).[UniProtKB:P03300] Involved in the viral replication complex and viral polypeptide maturation. It exhibits protease activity with a specificity and catalytic efficiency that is different from protease 3C. Protein 3CD lacks polymerase activity. Protein 3CD binds to the 5'UTR of the viral genome.[UniProtKB:P03300] Major viral protease that mediates proteolytic processing of the polyprotein (By similarity). Cleaves host EIF5B, contributing to host translation shutoff (By similarity). Cleaves also host PABPC1, contributing to host translation shutoff (By similarity). Disassembles host cytoplasmic stress granules by cleaving host G3BP1, although this effect is less prononced than the inhibition induced by protease 2A (By similarity). Cleaves host RIGI and thus contributes to the inhibition of type I interferon production (By similarity). Cleaves host IRF7 and thus contributes to the inhibition of type I interferon production (By similarity). Cleaves host HNRNPA1 thereby increasing the translation of apoptosis protease activating factor APAF1, leading to apoptosis of the host cell (By similarity). Cleaves host NLRP1, triggers host N-glycine-mediated degradation of the autoinhibitory NLRP1 N-terminal fragment (By similarity).[UniProtKB:P03300][UniProtKB:P03303][UniProtKB:Q66478] Replicates the viral genomic RNA on the surface of intracellular membranes. May form linear arrays of subunits that propagate along a strong head-to-tail interaction called interface-I. Covalently attaches UMP to a tyrosine of VPg, which is used to prime RNA synthesis. The positive stranded RNA genome is first replicated at virus induced membranous vesicles, creating a dsRNA genomic replication form. This dsRNA is then used as template to synthesize positive stranded RNA genomes. ss(+)RNA genomes are either translated, replicated or encapsidated.[UniProtKB:P03300] Publication Abstract from PubMedFor cryoelectron microscopy (cryo-EM), high cooling rates have been required for preparation of protein samples to vitrify the surrounding water and avoid formation of damaging crystalline ice. Whether and how crystalline ice affects single-particle cryo-EM is still unclear. Here, single-particle cryo-EM was used to analyze three-dimensional structures of various proteins and viruses embedded in crystalline ice formed at various cooling rates. Low cooling rates led to shrinkage deformation and density distortions on samples having loose structures. Higher cooling rates reduced deformations. Deformation-free proteins in crystalline ice were obtained by modifying the freezing conditions, and reconstructions from these samples revealed a marked improvement over vitreous ice. This procedure also increased the efficiency of cryo-EM structure determinations and was essential for high-resolution reconstructions. Addressing compressive deformation of proteins embedded in crystalline ice.,Shi H, Wu C, Zhang X Structure. 2023 Feb 2;31(2):213-220.e3. doi: 10.1016/j.str.2022.12.001. Epub 2022 , Dec 30. PMID:36586403[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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