Activation dynamics traced through a G protein-coupled receptor by 81 ¹H-¹⁵N NMR probes.

Authors

Feng-Jie Wu, Pascal S Rieder, Layara Akemi Abiko, Anne Grahl, Daniel Häussinger, Stephan Grzesiek

Published in

Science (New York, N.Y.). Volume 388. Issue 6748. Pages eadq9106. May 15, 2025. Epub May 15, 2025.

Abstract

The regulation of G protein-coupled receptor signaling by different orthosteric ligands is thought to occur through shifts in dynamically interconverting, conformational distributions. Such changes in dynamical distributions have been detected so far only by very sparse, often non-native experimental probes at low resolution. Using a recently developed paramagnetic nuclear magnetic resonance (NMR) method, we could assign and follow 81 ¹H-¹⁵N NMR correlations in the β₁-adrenergic receptor β₁AR at ambient conditions in response to various orthosteric ligands in the absence or presence of a G protein-mimicking nanobody. The comparison reveals the dynamics and mechanism of the central, highly conserved xWIPF₃ motif, contiguous regions of rigid and loose conformational coupling separated by conserved prolines during signal transmission, and the plasticity of the intracellular face in response to transducer binding.

PMID:
40373152
Bibliographic data and abstract were imported from PubMed on 16 May 2025.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.