3O45

Crystal Structure of 101F Fab Bound to 17-mer Peptide Epitope

Summary for 3O45

• Entry DOI: 10.2210/pdb3o45/pdb
• Related: 3O41
• Descriptor: Mouse monoclonal antibody 101F 101F Fab light chain, Mouse monoclonal antibody 101F 101F Fab heavy chain, Fusion glycoprotein F1, ... (5 entities in total)
• Functional Keywords: immunoglobulin, immune system-viral protein complex, immune system/viral protein
• Biological source: Mus musculus (mouse); More
• Cellular location: Virion membrane; Single-pass type I membrane protein: P03420
• Total number of polymer chains: 6
• Total formula weight: 99855.00

Authors

McLellan, J.S.,Chen, M.,Chang, J.S.,Yang, Y.,Kim, A.,Graham, B.S.,Kwong, P.D. (deposition date: 2010-07-26, release date: 2010-10-13, Last modification date: 2024-10-30)

Primary citation

McLellan, J.S.,Chen, M.,Chang, J.S.,Yang, Y.,Kim, A.,Graham, B.S.,Kwong, P.D.
Structure of a Major Antigenic Site on the Respiratory Syncytial Virus Fusion Glycoprotein in Complex with Neutralizing Antibody 101F.
J.Virol., 84:12236-12244, 2010

PubMed Abstract: Respiratory syncytial virus (RSV) is a major cause of pneumonia and bronchiolitis in infants and elderly people. Currently there is no effective vaccine against RSV, but passive prophylaxis with neutralizing antibodies reduces hospitalizations. To investigate the mechanism of antibody-mediated RSV neutralization, we undertook structure-function studies of monoclonal antibody 101F, which binds a linear epitope in the RSV fusion glycoprotein. Crystal structures of the 101F antigen-binding fragment in complex with peptides from the fusion glycoprotein defined both the extent of the linear epitope and the interactions of residues that are mutated in antibody escape variants. The structure allowed for modeling of 101F in complex with trimers of the fusion glycoprotein, and the resulting models suggested that 101F may contact additional surfaces located outside the linear epitope. This hypothesis was supported by surface plasmon resonance experiments that demonstrated 101F bound the peptide epitope ∼16,000-fold more weakly than the fusion glycoprotein. The modeling also showed no substantial clashes between 101F and the fusion glycoprotein in either the pre- or postfusion state, and cell-based assays indicated that 101F neutralization was not associated with blocking virus attachment. Collectively, these results provide a structural basis for RSV neutralization by antibodies that target a major antigenic site on the fusion glycoprotein.

PubMed: 20881049
DOI: 10.1128/JVI.01579-10

Experimental method

X-RAY DIFFRACTION (2.872 Å)