Catching a complex for optimal signaling [Protein Structure and Folding] (Journal of Biological Chemistry)

Agonistic antibodies are powerful tools to dimerize receptors in the absence of ligand binding, but high-fidelity receptor activation requires that these antibodies accurately recapitulate the native dimeric state. Spangler et al. employ a clever approach to select for antibodies that bind a specific IL-4R?/?c heterodimeric complex in its native signaling conformation, leading to a monovalent `stapler,` a single-chain variable fragment (scFv) that binds at the dimerization interface. This powerful approach can be further exploited for a variety of homo- or heterodimeric receptors to achieve signaling, especially in the absence of endogenous ligand.