A single‐domain intrabody targeting the follicle‐stimulating hormone receptor impacts FSH ‐induced G protein‐dependent signalling

Pauline Raynaud (1) , Vinesh Jugnarain (1) , Océane Vaugrente (1) , Amandine Vallet (1) , Thomas Boulo (1) , Camille Gauthier (1) , Asuka Inoue (2) , Nathalie Sibille (3) , Christophe Gauthier (1) , Frédéric Jean-Alphonse (4, 1) , Eric Reiter (4, 1) , Pascale Crépieux (4, 1) , Gilles Bruneau (1)

1 PRC - Physiologie de la reproduction et des comportements [Nouzilly]
2 Tohoku University [Sendai]
3 CBS - Centre de Biologie Structurale [Montpellier]
4 MUSCA - Dynamiques de populations multi-échelles pour des systèmes physiologiques

Intracellular variable fragments of heavy‐chain antibody from camelids (intra‐VHH) have been successfully used as chaperones to solve the 3D structure of active G protein‐coupled receptors bound to their transducers. However, their effect on signalling has been poorly explored, although they may provide a better understanding of the relationships between receptor conformation and activity. Here, we isolated and characterized iPRC1, the first intra‐VHH recognizing a member of the large glycoprotein hormone receptor family, the follicle‐stimulating hormone receptor (FSHR). This intra‐VHH recognizes the FSHR third intracellular loop and decreases cAMP production in response to FSH, without altering Gαs recruitment. Hence, iPRC1 behaves as an allosteric modulator and provides a new tool to complete structure/activity studies performed thus far on this receptor.

Mots clés: cell signalling; FSH receptor; FSH; GPCR; Intracellular VHHs

Domaines: Sciences du Vivant [q-bio]

Pauline Raynaud, Vinesh Jugnarain, Océane Vaugrente, Amandine Vallet, Thomas Boulo, et al.. A single‐domain intrabody targeting the follicle‐stimulating hormone receptor impacts FSH ‐induced G protein‐dependent signalling. FEBS Letters, 2024, 598 (2), pp.220-232. ⟨10.1002/1873-3468.14765⟩. ⟨hal-04564581⟩