PDBsum entry 4mmt

Viral protein

PDB id: 4mmt

Contents

Protein chains

73 a.a.

380 a.a.

PDB id:

4mmt

Name:

Viral protein

Title:

Crystal structure of prefusion-stabilized rsv f variant ds-cav1 at ph 9.5

Structure:

Fusion glycoprotein f2. Chain: a. Engineered: yes. Mutation: yes. Fusion glycoprotein f1 fused with fibritin trimerization domain. Chain: b. Engineered: yes. Mutation: yes

Source:

Human respiratory syncytial virus a2. Organism_taxid: 11259. Gene: f. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: freestyle(tm) 293-f. Human respiratory syncytial virus a2, enterobacteria phage t4. Organism_taxid: 11259, 10665.

Resolution:

3.05Å R-factor: 0.231 R-free: 0.243

Authors:

M.G.Joyce,J.S.Mclellan,G.B.E.Stewart-Jones,M.Sastry,Y.Yang, B.S.Graham,P.D.Kwong

Key ref:

J.S.McLellan et al. (2013). Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus. Science, 342, 592-598. PubMed id: 24179220 DOI: 10.1126/science.1243283

Date:

09-Sep-13 Release date: 20-Nov-13

Protein chain

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

Seq: 574 a.a.

Struc: 73 a.a.

Protein chain

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

Seq: 574 a.a.

Struc: 380 a.a.*

Protein chain

P10104  (WAC_BPT4) -  Fibritin from Enterobacteria phage T4

Seq: 487 a.a.

Struc: 380 a.a.*

* PDB and UniProt seqs differ at 327 residue positions (black crosses)

DOI no: 10.1126/science.1243283

Science 342:592-598 (2013)

PubMed id: 24179220

Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus.

J.S.McLellan, M.Chen, M.G.Joyce, M.Sastry, G.B.Stewart-Jones, Y.Yang, B.Zhang, L.Chen, S.Srivatsan, A.Zheng, T.Zhou, K.W.Graepel, A.Kumar, S.Moin, J.C.Boyington, G.Y.Chuang, C.Soto, U.Baxa, A.Q.Bakker, H.Spits, T.Beaumont, Z.Zheng, N.Xia, S.Y.Ko, J.P.Todd, S.Rao, B.S.Graham, P.D.Kwong.

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.