4fzh

Structure of the Ulster Strain Newcastle Disease Virus Hemagglutinin-Neuraminidase Reveals Auto-Inhibitory Interactions Associated with Low Virulence

spinqualitylabelsall models 4fzh, resolution 3.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4fzh is a 4 chain structure with sequence from Newcastle disease virus Ulster/67. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.5008Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HN_NDVU Attaches the virus to sialic acid-containing cell receptors and thereby initiating infection. Binding of HN protein to the receptor induces a conformational change that allows the F protein to trigger virion/cell membranes fusion (By similarity). Neuraminidase activity ensures the efficient spread of the virus by dissociating the mature virions from the neuraminic acid containing glycoproteins (By similarity). Publication Abstract from PubMed Paramyxovirus hemagglutinin-neuraminidase (HN) plays roles in viral entry and maturation, including binding to sialic acid receptors, activation of the F protein to drive membrane fusion, and enabling virion release during virus budding. HN can thereby directly influence virulence and in a subset of avirulent Newcastle disease virus (NDV) strains, such as NDV Ulster, HN must be proteolytically activated to remove a C-terminal extension not found in other NDV HN proteins. Ulster HN is 616 amino acids long and the 45 amino acid C-terminal extension present in its precursor (HN(0)) form has to be cleaved to render HN biologically active. Here we show that Ulster HN contains an inter-subunit disulfide bond within the C-terminal extension at residue 596, which regulates HN activities and neuraminidase (NA) domain dimerization. We determined the crystal structure of the dimerized NA domain containing the C-terminal extension, which extends along the outside of the sialidase beta-propeller domain and inserts C-terminal residues into the NA domain active site. The C-terminal extension also engages a secondary sialic acid binding site present in NDV HN proteins, which is located at the NA domain dimer interface, that most likely blocks its attachment function. These results clarify how the Ulster HN C-terminal residues lead to an auto-inhibited state of HN, the requirement for proteolytic activation of HN(0) and associated reduced virulence. Structure of the ulster strain newcastle disease virus hemagglutinin-neuraminidase reveals auto-inhibitory interactions associated with low virulence.,Yuan P, Paterson RG, Leser GP, Lamb RA, Jardetzky TS PLoS Pathog. 2012 Aug;8(8):e1002855. Epub 2012 Aug 9. PMID:22912577 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Hemagglutinin 3D structures

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