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Comment
. 2024 Jan;598(2):220-232.
doi: 10.1002/1873-3468.14765. Epub 2023 Nov 3.

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  1   4 , Eric Reiter  1   4 , Pascale Crépieux  1   4 , Gilles Bruneau  1
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Free article
Comment

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

Pauline Raynaud et al. FEBS Lett. 2024 Jan.
Free article

Abstract

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.

Keywords: FSH receptor; G protein-coupled receptors; cell signalling; intracellular VHH.

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Comment on

  • Intracellular VHHs to monitor and modulate GPCR signaling.
    Raynaud P, Gauthier C, Jugnarain V, Jean-Alphonse F, Reiter E, Bruneau G, Crépieux P. Raynaud P, et al. Front Endocrinol (Lausanne). 2022 Nov 16;13:1048601. doi: 10.3389/fendo.2022.1048601. eCollection 2022. Front Endocrinol (Lausanne). 2022. PMID: 36465650 Free PMC article. Review.

References

    1. Latorraca NR, Venkatakrishnan AJ and Dror RO (2017) GPCR dynamics: structures in motion. Chem Rev 117, 139-155.
    1. De Pascali F, Ayoub MA, Benevelli R, Sposini S, Lehoux J, Gallay N, Raynaud P, Landomiel F, Jean-Alphonse F, Gauthier C et al. (2021) Pharmacological characterization of low molecular weight biased agonists at the follicle stimulating hormone receptor. Int J Mol Sci 22, 9850.
    1. Stijlemans B, Conrath K, Cortez-Retamozo V, Van Xong H, Wyns L, Senter P, Revets H, De Baetselier P, Muyldermans S and Magez S (2004) Efficient targeting of conserved cryptic epitopes of infectious agents by single domain antibodies. J Biol Chem 279, 1256-1261.
    1. Liu H, Schittny V and Nash MA (2019) Removal of a conserved disulfide bond does not compromise mechanical stability of a VHH antibody complex. Nano Lett 19, 5524-5529.
    1. Manglik A and Kobilka B (2014) The role of protein dynamics in GPCR function: insights from the β2AR and rhodopsin. Curr Opin Cell Biol 27, 136-143.

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