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Seminar – Marina Casiraghi

19 October 2022 / 14:30

Marina Casiraghi

Venue : Salle Pyramide (Centre Broca Nouvelle-Aquitaine)

Marina Casiraghi
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus
Drive, Stanford, CA 94305, USA

Invited by Daniel Choquet


Investigation of Gprotein specificity and biased agonism at the beta2 adrenergic receptor (β 2AR)


The beta2adrenergic receptor (β2AR) is a prototypical Gprotein coupled receptor (GPCR). In cardiomyocytes, β2AR couples to the Gprotein subtypes Gs and Gi to regulate cardiac function. We used this system to investigate the molecular determinants of biased agonism and Gprotein specificity. We developed a Gibiased agonist, LM189, that we used to obtain
the cryoEM structure of the β2ARGi complex. Spectroscopic investigations show that distinct intermediate states, differentially stabilized by balanced and biased ligands, contribute to Gprotein specificity. Understanding the basis of specificity and bias is important to design safer drugs that target GPCRs with reduced side effects.

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19 October 2022
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