Department of Physiology and Biophysics, School of Life Sciences, Fudan University, Shanghai, China.
FEBS Lett. 2019 Jun;593(11):1248-1256. doi: 10.1002/1873-3468.13398. Epub 2019 May 20.
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 (CDR1) 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 CDR1. Our findings provide useful structural information for the further development and optimization of hapten-specific VHH antibodies.
迄今为止，仅有少数关于 VH H 抗体与低分子量半抗原结合的结构模型被报道。在此，我们报道了皮质醇与其 VHH 抗体 NbCor 在 pH 值为 3.5 和 10.5 时的结合晶体结构。皮质醇主要通过埋藏在 NbCor 的互补决定区 1（CDR1）形成的隧道中与 NbCor 结合。微尺度热泳分析也验证了 NbCor 与皮质醇和类似化合物的亲和力。将我们的发现与之前报道的几种半抗原-VHH 抗体复合物结构相结合，我们提出 VH H 抗体通过将小分子半抗原包裹在 CDR1 形成的隧道中，表现出一种结合小半抗原的特殊机制。我们的发现为进一步开发和优化针对半抗原的 VH H 抗体提供了有用的结构信息。
