PDBsum entry 5k6f

Viral protein

PDB id: 5k6f

Contents

Protein chain

450 a.a.

Waters ×57

PDB id:

5k6f

Name:

Viral protein

Title:

Crystal structure of prefusion-stabilized rsv f single-chain 9-19 ds- cav1 variant.

Structure:

Fusion glycoprotein f0. Chain: f. Fragment: unp residues 26-103 linked to residues 145-509 via linker residues ggsggsg. Synonym: protein f,protein f. Engineered: yes. Other_details: rsv f single-chain 9-19 ds-cav1 variant

Source:

Human respiratory syncytial virus a (strain a2). Organism_taxid: 11259. Strain: a2. Expressed in: homo sapiens. Expression_system_taxid: 9606

Resolution:

2.59Å R-factor: 0.204 R-free: 0.237

Authors:

M.G.Joyce,B.Zhang,Y.T.Lai,J.R.Mascola,P.D.Kwong

Key ref:

M.G.Joyce et al. (2016). Iterative structure-based improvement of a fusion-glycoprotein vaccine against RSV. Nat Struct Biol, 23, 811-820. PubMed id: 27478931 DOI: 10.1038/nsmb.3267

Date:

24-May-16 Release date: 10-Aug-16

Protein chain

P03420  (FUS_HRSVA) -  Fusion glycoprotein F0 from Human respiratory syncytial virus A (strain A2)

Seq: 574 a.a.

Struc: 450 a.a.*

* PDB and UniProt seqs differ at 14 residue positions (black crosses)

DOI no: 10.1038/nsmb.3267

Nat Struct Biol 23:811-820 (2016)

PubMed id: 27478931

Iterative structure-based improvement of a fusion-glycoprotein vaccine against RSV.

M.G.Joyce, B.Zhang, L.Ou, M.Chen, G.Y.Chuang, A.Druz, W.P.Kong, Y.T.Lai, E.J.Rundlet, Y.Tsybovsky, Y.Yang, I.S.Georgiev, M.Guttman, C.R.Lees, M.Pancera, M.Sastry, C.Soto, G.B.Stewart-Jones, P.V.Thomas, J.G.Van Galen, U.Baxa, K.K.Lee, J.R.Mascola, B.S.Graham, P.D.Kwong.

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.