1frg
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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
OverviewOverview
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.
About this StructureAbout this Structure
1FRG is a Protein complex structure of sequences from [1] with ACE and NH2 as ligands. Full crystallographic information is available from OCA.
ReferenceReference
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., Churchill ME, Stura EA, Pinilla C, Appel JR, Houghten RA, Kono DH, Balderas RS, Fieser GG, Schulze-Gahmen U, Wilson IA, J Mol Biol. 1994 Aug 26;241(4):534-56. PMID:7520084
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