8jmt
Structure of the adhesion GPCR ADGRL3 in the apo state
Structural highlights
FunctionC562_ECOLX Electron-transport protein of unknown function.AGRL3_HUMAN Plays a role in cell-cell adhesion and neuron guidance via its interactions with FLRT2 and FLRT3 that are expressed at the surface of adjacent cells (PubMed:26235030). Plays a role in the development of glutamatergic synapses in the cortex. Important in determining the connectivity rates between the principal neurons in the cortex.[UniProtKB:Q80TS3][1] Publication Abstract from PubMedG-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 beta(2)-adrenergic receptor (beta(2)AR) bound to antagonistic and agonistic ligands and the adhesion GPCR ADGRL3 in the apo state. For beta(2)AR, 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 structureâfunction relationships and drug development. A method for structure determination of GPCRs in various states.,Guo Q, He B, Zhong Y, Jiao H, Ren Y, Wang Q, Ge Q, Gao Y, Liu X, Du Y, Hu H, Tao Y Nat Chem Biol. 2024 Jan;20(1):74-82. doi: 10.1038/s41589-023-01389-0. Epub 2023 , Aug 14. PMID:37580554[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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