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Updated: Jul 26, 2025

Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET
Published on: August 17, 2022
7TM domain structures of adhesion GPCRs: what's new and what's missing?
Florian Seufert1, Yin Kwan Chung2, Peter W Hildebrand3
1Institute of Medical Physics and Biophysics, Medical Faculty, Leipzig University, Härtelstrasse 16-18, 04107 Leipzig, Germany.
Abstract:
Adhesion-type G protein-coupled receptors (aGPCRs) have long resisted approaches to resolve the structural details of their heptahelical transmembrane (7TM) domains. Single-particle cryogenic electron microscopy (cryo-EM) has recently produced aGPCR 7TM domain structures for ADGRD1, ADGRG1, ADGRG2, ADGRG3, ADGRG4, ADGRG5, ADGRF1, and ADGRL3. We review the unique properties, including the position and conformation of their activating tethered agonist (TA) and signaling motifs within the 7TM bundle, that the novel structures have helped to identify. We also discuss questions that the kaleidoscope of novel aGPCR 7TM domain structures have left unanswered. These concern the relative positions, orientations, and interactions of the 7TM and GPCR autoproteolysis-inducing (GAIN) domains with one another. Clarifying their interplay remains an important goal of future structural studies on aGPCRs.
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