4zpt

Structure of MERS-Coronavirus Spike Receptor-binding Domain (England1 Strain) in Complex with Vaccine-Elicited Murine Neutralizing Antibody D12 (Crystal Form 1)Structure of MERS-Coronavirus Spike Receptor-binding Domain (England1 Strain) in Complex with Vaccine-Elicited Murine Neutralizing Antibody D12 (Crystal Form 1)

Structural highlights 4zpt is a 6 chain structure with sequence from Betacoronavirus england 1 and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Related: 4kr0, 4zpv, 4zpw Gene: S, 3 (Betacoronavirus England 1) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [SPIKE_CVEMC] S1 attaches the virion to the cell membrane by interacting with host DPP4, initiating the infection. S2 is a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and plasma cell membranes (By similarity). Publication Abstract from PubMed The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development. Evaluation of candidate vaccine approaches for MERS-CoV.,Wang L, Shi W, Joyce MG, Modjarrad K, Zhang Y, Leung K, Lees CR, Zhou T, Yassine HM, Kanekiyo M, Yang ZY, Chen X, Becker MM, Freeman M, Vogel L, Johnson JC, Olinger G, Todd JP, Bagci U, Solomon J, Mollura DJ, Hensley L, Jahrling P, Denison MR, Rao SS, Subbarao K, Kwong PD, Mascola JR, Kong WP, Graham BS Nat Commun. 2015 Jul 28;6:7712. doi: 10.1038/ncomms8712. PMID:26218507 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 4zpt, resolution 2.59Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image