Structure of an anti-cholera toxin antibody Fab in complex with an epitope-derived D-peptide: a case of polyspecific recognition.
The structure of a complex of the anti-cholera toxin antibody TE33 Fab (fragment antibody) with the D-peptide vpGsqhyds was solved to 1.78 A resolution. The D-peptide was derived from the linear L-peptide epitope VPGSQHIDS by a stepwise transformation. Despite the very similar amino acid sequence-the only difference is a tyrosine residue in position 7-there are marked differences in the individual positions with respect to their contribution to the peptide overall affinity as ascertained by a complete substitutional analysis. This is reflected by the X-ray structure of the TE33 Fab/D-peptide complex where there is an inverted orientation of the D-peptide as compared with the known structure of a corresponding complex containing the epitope L-peptide, with the side chains establishing different contacts within the binding site of TE33. The D- and L-peptide affinities are comparable and the surface areas buried by complex formation are almost the same. Thus the antibody TE33 provides a typical example for polyspecific binding behavior of IgG family antibodies.
Scheerer
Patrick
P
Charité-Universitätsmedizin Berlin, Institute of Biochemistry, Monbijoustr. 2, D-10117 Berlin, Germany.
Kramer
Achim
A
Otte
Livia
L
Seifert
Martina
M
Wessner
Helga
H
Scholz
Christa
C
Krauss
Norbert
N
Schneider-Mergener
Jens
J
Höhne
Wolfgang
W
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex / Q000032:analysis / Q000737:chemistry*; D001666:Binding Sites, Antibody; D002772:Cholera Toxin / Q000276:immunology*; D003429:Cross Reactions; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000737:chemistry / Q000378:metabolism*; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary
D000936:Antigen-Antibody Complex; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D002772:Cholera Toxin