title: Antigen recognition by conformational selection.
abstract: 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.
authors.affiliation: Biochemisches Institut der Universität, Zürich, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Berger
authors.forename: S
authors.initials: S
authors.lastname: Weber-Bornhauser
authors.forename: J
authors.initials: J
authors.lastname: Eggenberger
authors.forename: J
authors.initials: J
authors.lastname: Hanes
authors.forename: A
authors.initials: A
authors.lastname: Plückthun
authors.forename: H R
authors.initials: HR
authors.lastname: Bosshard
mesh_terms: 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
chemical_list: D000906:Antibodies; D000941:Antigens; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D007128:Immunoglobulin Fragments; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases