1FRG

CRYSTAL STRUCTURE, SEQUENCE, AND EPITOPE MAPPING OF A PEPTIDE COMPLEX OF AN ANTI-INFLUENZA HA PEPTIDE ANTIBODY FAB 26(SLASH)9: FINE-TUNING ANTIBODY SPECIFICITY

Summary for 1FRG

• Entry DOI: 10.2210/pdb1frg/pdb
• Related: 1HIM 1HIN 1IFH
• Descriptor: IGG2A 26/9 FAB (LIGHT CHAIN), IGG2A 26/9 FAB (HEAVY CHAIN), INFLUENZA HEMAGGLUTININ HA1 (STRAIN X47) (RESIDUES 101 - 108), ... (4 entities in total)
• Functional Keywords: immunoglobulin/virus hemagglutinin, viral protein-immune system complex, viral protein/immune system
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 3
• Total formula weight: 48688.33

Authors

Churchill, M.E.A.,Wilson, I.A. (deposition date: 1994-01-17, release date: 1994-05-31, Last modification date: 2024-10-30)

Primary citation

Churchill, M.E.,Stura, E.A.,Pinilla, C.,Appel, J.R.,Houghten, R.A.,Kono, D.H.,Balderas, R.S.,Fieser, G.G.,Schulze-Gahmen, U.,Wilson, I.A.
Crystal structure of a peptide complex of anti-influenza peptide antibody Fab 26/9. Comparison of two different antibodies bound to the same peptide antigen.
J.Mol.Biol., 241:534-556, 1994

PubMed Abstract: The three-dimensional structure of the complex of a second anti-peptide antibody (Fab 26/9) that recognizes the same six-residue epitope of an immunogenic peptide from influenza virus hemagglutinin (HA1; 75-110) as Fab 17/9 with the peptide has been determined at 2.8 A resolution. The amino acid sequence of the variable region of the 26/9 antibody differs in 24 positions from that of 17/9, the first antibody in this series for which several ligand-bound and free structures have been determined and refined. Comparison of the 26/9-peptide with the 17/9-peptide complex structures shows that the two Fabs are very similar (r.m.s.d. 0.5 to 0.8 A) and that the peptide antigen (101-107) has virtually the same conformation (r.m.s.d. 0.3 to 0.8 A) when bound to both antibodies. A sequence difference in the 26/9 binding pocket (L94; His in 26/9, Asn in 17/9) results in an interaction with a bound water molecule that is not seen in the 17/9 structures. Epitope mapping shows that the relative specificity of 26/9 and 17/9 antibodies for individual positions of the peptide antigen are slightly different. Amino acid substitutions in the peptide, particularly at position SerP107, are tolerated to different extents by 17/9 and 26/9. Structural and sequence analysis suggests that amino acid differences near the peptide-binding site are responsible for altering slightly the specificity of 26/9 for three peptide residues and illustrates how amino acid substitutions can modify antibody-antigen interactions and thereby modulate antibody specificity.

PubMed: 7520084
DOI: 10.1006/jmbi.1994.1530

Experimental method

X-RAY DIFFRACTION (2.8 Å)