8JMT

Structure of the adhesion GPCR ADGRL3 in the apo state

Summary for 8JMT

• Entry DOI: 10.2210/pdb8jmt/pdb
• EMDB information: 36426
• Descriptor: Adhesion G protein-coupled receptor L3,Soluble cytochrome b562 (1 entity in total)
• Functional Keywords: adgrl3, apo form, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 1
• Total formula weight: 85439.92

Authors

Tao, Y.,Guo, Q.,He, B.,Zhong, Y. (deposition date: 2023-06-05, release date: 2023-09-06, Last modification date: 2025-07-02)

Primary citation

Guo, Q.,He, B.,Zhong, Y.,Jiao, H.,Ren, Y.,Wang, Q.,Ge, Q.,Gao, Y.,Liu, X.,Du, Y.,Hu, H.,Tao, Y.
A method for structure determination of GPCRs in various states.
Nat.Chem.Biol., 20:74-82, 2024

PubMed Abstract: G-protein-coupled receptors (GPCRs) are a class of integral membrane proteins that detect environmental cues and trigger cellular responses. Deciphering the functional states of GPCRs induced by various ligands has been one of the primary goals in the field. Here we developed an effective universal method for GPCR cryo-electron microscopy structure determination without the need to prepare GPCR-signaling protein complexes. Using this method, we successfully solved the structures of the β-adrenergic receptor (βAR) bound to antagonistic and agonistic ligands and the adhesion GPCR ADGRL3 in the apo state. For βAR, an intermediate state stabilized by the partial agonist was captured. For ADGRL3, the structure revealed that inactive ADGRL3 adopts a compact fold and that large unusual conformational changes on both the extracellular and intracellular sides are required for activation of adhesion GPCRs. We anticipate that this method will open a new avenue for understanding GPCR structure‒function relationships and drug development.

PubMed: 37580554
DOI: 10.1038/s41589-023-01389-0

Experimental method

ELECTRON MICROSCOPY (3.36 Å)