EMD-20572

Single-particle
4.1 Å
EMD-20572 Deposition: 08/08/2019
Map released: 02/10/2019
Last modified: 09/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-20572

Cryo-EM structure of extracellular dimeric complex of RET/GFRAL/GDF15

EMD-20572

Single-particle
4.1 Å
EMD-20572 Deposition: 08/08/2019
Map released: 02/10/2019
Last modified: 09/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: RET, GFRAL and GDF15 extracellular complex
Fitted models: 6q2j (Avg. Q-score: 0.111)

Deposition Authors: Li J , Shang GJ
Cryo-EM analyses reveal the common mechanism and diversification in the activation of RET by different ligands.
Li J , Shang G , Chen YJ, Brautigam CA , Liou J , Zhang X , Bai XC
(2019) eLife , 8
PUBMED: 31535977
DOI: doi:10.7554/eLife.47650
ISSN: 2050-084X
Abstract:
RET is a receptor tyrosine kinase (RTK) that plays essential roles in development and has been implicated in several human diseases. Different from most of RTKs, RET requires not only its cognate ligands but also co-receptors for activation, the mechanisms of which remain unclear due to lack of high-resolution structures of the ligand/co-receptor/receptor complexes. Here, we report cryo-EM structures of the extracellular region ternary complexes of GDF15/GFRAL/RET, GDNF/GFRα1/RET, NRTN/GFRα2/RET and ARTN/GFRα3/RET. These structures reveal that all the four ligand/co-receptor pairs, while using different atomic interactions, induce a specific dimerization mode of RET that is poised to bring the two kinase domains into close proximity for cross-phosphorylation. The NRTN/GFRα2/RET dimeric complex further pack into a tetrameric assembly, which is shown by our cell-based assays to regulate the endocytosis of RET. Our analyses therefore reveal both the common mechanism and diversification in the activation of RET by different ligands.