TY - JOUR
T1 - Antibody recognition of disordered antigens
AU - Macraild, Christopher A
AU - Richards, Jack S
AU - Anders, Robin F
AU - Norton, Raymond S
PY - 2016/1/5
Y1 - 2016/1/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84953280746&partnerID=8YFLogxK
UR - http://ac.els-cdn.com.ezproxy.lib.monash.edu.au/S0969212615004700/1-s2.0-S0969212615004700-main.pdf?_tid=43d4d34c-68f4-11e6-802a-00000aab0f6c&acdnat=1471931080_6a1b20fadba17f4e6d027a4e08af6dd4
U2 - 10.1016/j.str.2015.10.028
DO - 10.1016/j.str.2015.10.028
M3 - Article
AN - SCOPUS:84953280746
SN - 0969-2126
VL - 24
SP - 148
EP - 157
JO - Structure
JF - Structure
IS - 1
ER -