5K6H

Crystal structure of prefusion-stabilized RSV F single-chain 9-10 DS-Cav1 A149C-Y458C variant.

Summary for 5K6H

• Entry DOI: 10.2210/pdb5k6h/pdb
• Related: 5K6B 5K6C 5K6F 5K6G 5K6I
• Descriptor: Fusion glycoprotein F0 (2 entities in total)
• Functional Keywords: respiratory syncytial virus, prefusion, vaccine, stabilized, viral protein
• Biological source: Human respiratory syncytial virus A (strain A2)
• Cellular location: Virion membrane; Single-pass type I membrane protein: P03420
• Total number of polymer chains: 1
• Total formula weight: 49217.16

Authors

Joyce, M.G.,Zhang, B.,Mascola, J.R.,Kwong, P.D. (deposition date: 2016-05-24, release date: 2016-09-21, Last modification date: 2024-11-06)

Primary citation

Joyce, M.G.,Zhang, B.,Ou, L.,Chen, M.,Chuang, G.Y.,Druz, A.,Kong, W.P.,Lai, Y.T.,Rundlet, E.J.,Tsybovsky, Y.,Yang, Y.,Georgiev, I.S.,Guttman, M.,Lees, C.R.,Pancera, M.,Sastry, M.,Soto, C.,Stewart-Jones, G.B.,Thomas, P.V.,Van Galen, J.G.,Baxa, U.,Lee, K.K.,Mascola, J.R.,Graham, B.S.,Kwong, P.D.
Iterative structure-based improvement of a fusion-glycoprotein vaccine against RSV.
Nat.Struct.Mol.Biol., 23:811-820, 2016

PubMed Abstract: Structure-based design of vaccines, particularly the iterative optimization used so successfully in the structure-based design of drugs, has been a long-sought goal. We previously developed a first-generation vaccine antigen called DS-Cav1, comprising a prefusion-stabilized form of the fusion (F) glycoprotein, which elicits high-titer protective responses against respiratory syncytial virus (RSV) in mice and macaques. Here we report the improvement of DS-Cav1 through iterative cycles of structure-based design that significantly increased the titer of RSV-protective responses. The resultant second-generation 'DS2'-stabilized immunogens have their F subunits genetically linked, their fusion peptides deleted and their interprotomer movements stabilized by an additional disulfide bond. These DS2 immunogens are promising vaccine candidates with superior attributes, such as their lack of a requirement for furin cleavage and their increased antigenic stability against heat inactivation. The iterative structure-based improvement described here may have utility in the optimization of other vaccine antigens.

PubMed: 27478931
DOI: 10.1038/nsmb.3267

Experimental method

X-RAY DIFFRACTION (2.648 Å)