Agonist-specific conformational dynamics at the β

Authors

• Sushrut D Shah
• Joshua Richard
• Suvankar Ghosh
• Jillian Jerwick
• Joice T Gavali
• Raymond B Penn
• Alexander D MacKerell
• Deepak A Deshpande

Publication/Presentation Date

9-1-2026

Abstract

BACKGROUND AND PURPOSE: β

EXPERIMENTAL APPROACH: The effects of a positive AM (PAM37) and two negative AMs (NAM36 and NAM42) were examined on β-agonist-induced Gαs and β-arrestin recruitment and downstream signalling (cAMP, PKA and ERK) in HEK293 cells expressing β

KEY RESULTS: PAM37 enhanced, whereas NAMs attenuated β

CONCLUSIONS AND IMPLICATIONS: These findings establish orthosteric ligand-dependent allostery as a fundamental feature of β

Volume

183

Issue

17

First Page

5315

Last Page

5335

ISSN

1476-5381

Published In/Presented At

Shah, S. D., Richard, J., Ghosh, S., Jerwick, J., Gavali, J. T., Penn, R. B., MacKerell, A. D., Jr, & Deshpande, D. A. (2026). Agonist-specific conformational dynamics at the β2-adrenoceptor dictate allosteric modulation of Gαs signalling and bronchodilation. British journal of pharmacology, 183(17), 5315–5335. https://doi.org/10.1111/bph.70513

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

42252113

Department(s)

Administration and Leadership

Document Type

Article