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Structural insights into the mechanism of single domain VHH antibody binding to cortisol
Author(s) -
Ding Lulu,
Wang Ziying,
Zhong Peiyu,
Jiang He,
Zhao Zhixuan,
Zhang Yiran,
Ren Zhen,
Ding Yu
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13398
Subject(s) - single domain antibody , chemistry , antibody , mechanism (biology) , biophysics , biology , immunology , physics , quantum mechanics
To date, few structural models of VHH antibody binding to low molecular weight haptens have been reported. Here, we report the crystal structure of cortisol binding to its VHH antibody NbCor at pH 3.5 and 10.5. Cortisol binds to NbCor mainly by burying itself under the tunnel formed by the complementarity determining region 1 ( CDR 1) of NbCor. The affinity of NbCor binding to cortisol and similar compounds was also verified by a microscale thermophoresis assay. Combining our findings with several previously reported structures of hapten‐ VHH antibody complexes, we propose that VHH antibodies exhibit a special mechanism of binding small haptens by encapsulating them in a tunnel formed by CDR 1. Our findings provide useful structural information for the further development and optimization of hapten‐specific VHH antibodies.