Engineering Nanobody Conformational Switches

Engineered nanobody variants that are partially unfolded until ligand binding fold exclusively upon target recognition, enabling conformational receptor switches for chorionic gonadotropin, tumor necrosis factor alpha, and methotrexate.

• Why it matters: Conformational signaling is powerful but hard to design into proteins; this work addresses the need for a general, tunable strategy to create ligand-gated receptors and sensors.
• What they did: The team introduced destabilizing framework mutations to tune nanobody stability while preserving molecular recognition, then engineered ligand-induced folding switches for three biomarkers/drugs and built an optical urine sensor for chorionic gonadotropin.
• The result: Ligand-gated conformational signaling directly gates signal transduction in the sensor and supports allosteric modulation of binding to control affinity and dynamic range, suggesting broad applicability to other target ligands.

AI summary of the abstract · may contain errors · not medical advice · read the paper.