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4MMU

Crystal Structure of Prefusion-stabilized RSV F Variant DS-Cav1 at pH 5.5

Summary for 4MMU
Entry DOI10.2210/pdb4mmu/pdb
Related4JHW 4MMQ 4MMR 4MMS 4MMT 4MMV
DescriptorFusion glycoprotein F2, Fusion glycoprotein F1 fused with Fibritin trimerization domain, SULFATE ION, ... (6 entities in total)
Functional Keywordsfusion, membrane, viral protein, structure-based vaccine design
Biological sourceHuman respiratory syncytial virus A2
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Total number of polymer chains2
Total formula weight55524.99
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: 2023-09-20)
Primary citationMcLellan, 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: 24179220
DOI: 10.1126/science.1243283
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (3 Å)
Structure validation

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