IBody-mediated tuning of synthetic cytokine receptor activation via rational nanobody interface engineering.

ABSTRACT: Nanobodies are small, single-domain antibody fragments derived from heavy chain-only antibodies. They combine high binding affinity with advantages such as compact size, stability, solubility, and flexible epitope recognition, making them attractive tools in molecular biology and therapeutic applications. In this study, we engineered and optimized nanobodies for controlled activation of synthetic cytokine receptors, aiming to expand options for receptor customization. Specifically, we used nanobodies as extracellular domains of the gp130 receptor to induce dimerization upon antigen binding. To enable receptor activity, we introduced framework mutations that promote the formation of an i-shaped nanobody (iBody) dimer, adapted from i-shaped antibodies. These mutations enhanced dimerization a

SUBMITTER: Kunze R 

PROVIDER: S-EPMC12477867 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature