Structure of the vasopressin hormone-V2 receptor-β-arrestin1 ternary complex

Bous, J.; Fouillen, A.; Orcel, H.; Trapani, S.; Cong, X.; Fontanel, S.; Saint-Paul, J.; LAI KEE HIM, J.; Urbach, S.; Sibille, N.; SOUNIER, R.; Granier, S.; Mouillac, B.; Bron, P.

doi:10.1101/2022.02.11.480047

bioRxiv · 10.1101/2022.02.11.480047

Structure of the vasopressin hormone-V2 receptor-β-arrestin1 ternary complex

Bous, J.·Fouillen, A.·Orcel, H.·Trapani, S.·Cong, X.·Fontanel, S.·Saint-Paul, J.·LAI KEE HIM, J.·Urbach, S.·Sibille, N.·SOUNIER, R.·Granier, S.·Mouillac, B.·Bron, P.

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Abstract

Arrestins interact with G protein-coupled receptors (GPCRs) to stop G protein activation and to initiate key signaling pathways. Recent structural studies shed light on the molecular mechanisms involved in GPCR-arrestin coupling, but whether this process is conserved among GPCRs is poorly understood. Here, we report the cryo-electron microscopy active structure of the wild-type arginine-vasopressin V2 receptor (V2R) in complex with {beta}-arrestin1. It reveals an atypical position of {beta}-arrestin1 compared to previously described GPCR-arrestin assemblies, associated with an original V2R/{beta}-arrestin1 interface involving all receptor intracellular loops. Phosphorylated sites of the V2R C-terminus are clearly identified and interact extensively with the {beta}-arrestin1 N-lobe, in agreement with structural data obtained with chimeric or synthetic systems. Overall, these findings highlight a striking structural variability among GPCR-arrestin signaling complexes.

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Bous, J., Fouillen, A., Orcel, H., Trapani, S., Cong, X., Fontanel, S., Saint-Paul, J., LAI KEE HIM, J., Urbach, S., Sibille, N., SOUNIER, R., Granier, S., Mouillac, B., Bron, P.. 2022-02-11. Structure of the vasopressin hormone-V2 receptor-β-arrestin1 ternary complex. https://doi.org/10.1101/2022.02.11.480047

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