Antibody recognition of disordered antigens

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)148-157
Number of pages10
JournalStructure
Volume24
Issue number1
DOIs
Publication statusPublished - 5 Jan 2016

Cite this

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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.",
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Antibody recognition of disordered antigens. / Macraild, Christopher A; Richards, Jack S; Anders, Robin F; Norton, Raymond S.

In: Structure, Vol. 24, No. 1, 05.01.2016, p. 148-157.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Macraild, Christopher A

AU - Richards, Jack S

AU - Anders, Robin F

AU - Norton, Raymond S

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