4MMT
Crystal Structure of Prefusion-stabilized RSV F Variant DS-Cav1 at pH 9.5
Summary for 4MMT
| Entry DOI | 10.2210/pdb4mmt/pdb |
| Related | 4JHW 4MMQ 4MMR 4MMS 4MMU 4MMV |
| Descriptor | Fusion glycoprotein F2, Fusion glycoprotein F1 fused with Fibritin trimerization domain (2 entities in total) |
| Functional Keywords | fusion, membrane, viral protein, structure-based vaccine design |
| Biological source | Human respiratory syncytial virus A2 More |
| Cellular location | Virion membrane; Single-pass type I membrane protein: P03420 Virion : P10104 |
| Total number of polymer chains | 2 |
| Total formula weight | 54824.56 |
| Authors | Joyce, M.G.,Mclellan, J.S.,Stewart-Jones, G.B.E.,Sastry, M.,Yang, Y.,Graham, B.S.,Kwong, P.D. (deposition date: 2013-09-09, release date: 2013-11-20, Last modification date: 2024-10-30) |
| Primary citation | McLellan, J.S.,Chen, M.,Joyce, M.G.,Sastry, M.,Stewart-Jones, G.B.,Yang, Y.,Zhang, B.,Chen, L.,Srivatsan, S.,Zheng, A.,Zhou, T.,Graepel, K.W.,Kumar, A.,Moin, S.,Boyington, J.C.,Chuang, G.Y.,Soto, C.,Baxa, U.,Bakker, A.Q.,Spits, H.,Beaumont, T.,Zheng, Z.,Xia, N.,Ko, S.Y.,Todd, J.P.,Rao, S.,Graham, B.S.,Kwong, P.D. Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus. Science, 342:592-598, 2013 Cited by PubMed Abstract: Respiratory syncytial virus (RSV) is the leading cause of hospitalization for children under 5 years of age. We sought to engineer a viral antigen that provides greater protection than currently available vaccines and focused on antigenic site Ø, a metastable site specific to the prefusion state of the RSV fusion (F) glycoprotein, as this site is targeted by extremely potent RSV-neutralizing antibodies. Structure-based design yielded stabilized versions of RSV F that maintained antigenic site Ø when exposed to extremes of pH, osmolality, and temperature. Six RSV F crystal structures provided atomic-level data on how introduced cysteine residues and filled hydrophobic cavities improved stability. Immunization with site Ø-stabilized variants of RSV F in mice and macaques elicited levels of RSV-specific neutralizing activity many times the protective threshold. PubMed: 24179220DOI: 10.1126/science.1243283 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.05 Å) |
Structure validation
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