A single domain intrabody targeting the follicle-stimulating hormone receptor (FSHR) impacts FSH-induced G protein-dependent signalling

Raynaud, P.; Jugnarain, V.; Vaugrente, O.; Vallet, A.; Boulo, T.; Gauthier, C.; Jean-Alphonse, F.; Reiter, E.; Crepieux, P.; Bruneau, G.

doi:10.1101/2023.08.07.552286

bioRxiv · 10.1101/2023.08.07.552286

A single domain intrabody targeting the follicle-stimulating hormone receptor (FSHR) impacts FSH-induced G protein-dependent signalling

Raynaud, P.·Jugnarain, V.·Vaugrente, O.·Vallet, A.·Boulo, T.·Gauthier, C.·Jean-Alphonse, F.·Reiter, E.·Crepieux, P.·Bruneau, G.

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Abstract

Intracellular variable fragments from 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 on 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 receptors family, the follicle-stimulating hormone receptor (FSHR). This intra-VHH recognizes the FSHR 3rd intracellular loop and decreases cAMP production in response to FSH, without altering Gs recruitment. Hence, iPRC1 behaves as an allosteric modulator and provides a new tool to complete structure/activity studies performed so far on this receptor.

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Raynaud, P., Jugnarain, V., Vaugrente, O., Vallet, A., Boulo, T., Gauthier, C., Jean-Alphonse, F., Reiter, E., Crepieux, P., Bruneau, G.. 2023-08-07. A single domain intrabody targeting the follicle-stimulating hormone receptor (FSHR) impacts FSH-induced G protein-dependent signalling. https://doi.org/10.1101/2023.08.07.552286

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