Antigen recognition by conformational selection.
Conformational adaptation between antigen and antibody can modulate the antibody specificity. The phenomenon has often been proposed to result from an 'induced fit', which implies that the binding reaction induces a conformational change in the antigen and the antibody. Thus, an 'induced fit' requires initial complex formation followed by a conformational change in the complex. However, an antibody may select those antigen molecules that happen to be in a fitting conformational state. This leads to the same end result as an induced fit. Here, we demonstrate conformational selection by a single chain antibody fragment, raised against a random coil variant of the leucine zipper domain of transcription factor GCN4, when it cross-reacts with the wild-type dimeric leucine zipper. Kinetic and equilibrium data show that the single chain antibody fragment fragment selects monomeric peptides from the population in equilibrium with the leucine zipper dimer.
Berger
C
C
Biochemisches Institut der Universität, Zürich, Switzerland.
Weber-Bornhauser
S
S
Eggenberger
J
J
Hanes
J
J
Plückthun
A
A
Bosshard
H R
HR
D000595:Amino Acid Sequence; D000906:Antibodies / Q000737:chemistry* / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology*; D000941:Antigens / Q000737:chemistry / Q000276:immunology*; D002942:Circular Dichroism; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000276:immunology; D007128:Immunoglobulin Fragments / Q000737:chemistry / Q000276:immunology; D007700:Kinetics; D016350:Leucine Zippers / Q000276:immunology; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011494:Protein Kinases / Q000276:immunology; D029701:Saccharomyces cerevisiae Proteins; D013816:Thermodynamics
D000906:Antibodies; D000941:Antigens; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D007128:Immunoglobulin Fragments; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases