title: Antibody Recognition of Disordered Antigens.
abstract: Disordered proteins are important antigens in a range of infectious diseases. Little is known, however, about the molecular details of recognition of disordered antigens by their cognate antibodies. Using a large dataset of protein antigens, we show that disordered epitopes are as likely to be recognized by antibodies as ordered epitopes. Moreover, the affinity with which antigens are recognized is, unexpectedly, only weakly dependent on the degree of disorder within the epitope. Structurally defined complexes of ordered and disordered protein antigens with their cognate antibodies reveal that disordered epitopes are smaller than their ordered counterparts, but are more efficient in their interactions with antibody. Our results demonstrate that disordered antigens are bona fide targets of antibody recognition, and that recognition of disordered epitopes is particularly sensitive to epitope variation, a finding with implications for the effects of disorder on the specificity of molecular recognition more generally.
authors.affiliation: Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia. Electronic address: chris.macraild@monash.edu.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: MacRaild
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, VIC 3004, Australia.
authors.forename: Jack S
authors.initials: JS
authors.lastname: Richards
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
authors.forename: Robin F
authors.initials: RF
authors.lastname: Anders
authors.affiliation: Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Norton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000936:Antigen-Antibody Complex / Q000737:chemistry*; D000939:Epitopes / Q000737:chemistry*; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding
chemical_list: D000936:Antigen-Antibody Complex; D000939:Epitopes; D064267:Intrinsically Disordered Proteins