Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Cryo-EM analyses reveal the common mechanism and diversification in the activation of RET by different ligands.
Journal, issue, pages	Elife, Vol. 8, Year 2019
Publish date	Sep 19, 2019
Authors	Jie Li / Guijun Shang / Yu-Ju Chen / Chad A Brautigam / Jen Liou / Xuewu Zhang / Xiao-Chen Bai /
PubMed 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 ...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.
External links	Elife / PubMed:31535977 / PubMed Central
Methods	EM (single particle)
Resolution	3.4 - 4.4 Å
Structure data	20572 6q2j EMDB-20572, PDB-6q2j: Cryo-EM structure of extracellular dimeric complex of RET/GFRAL/GDF15 Method: EM (single particle) / Resolution: 4.1 Å EMDB-20573: Cryo-EM structure of RET/GFRAL/GDF15 extracellular complex. The 3D refinement was focused on one of two halves with C1 symmetry applied. Method: EM (single particle) / Resolution: 3.7 Å 20575 6q2n EMDB-20575, PDB-6q2n: Cryo-EM structure of RET/GFRa1/GDNF extracellular complex Method: EM (single particle) / Resolution: 4.4 Å 20576 6q2o EMDB-20576, PDB-6q2o: Cryo-EM structure of RET/GFRa2/NRTN extracellular complex. The 3D refinement was applied with C2 symmetry. Method: EM (single particle) / Resolution: 3.65 Å EMDB-20577: Cryo-EM structure of RET/GFRa2/NRTN extracellular complex. The 3D refinement was focused on one of two halves with C1 symmetry applied. Method: EM (single particle) / Resolution: 3.4 Å 20578 6q2r EMDB-20578, PDB-6q2r: Cryo-EM structure of RET/GFRa2/NRTN extracellular complex in the tetrameric form Method: EM (single particle) / Resolution: 4.3 Å 20579 6q2s EMDB-20579: Cryo-EM structure of RET/GFRa3/ARTN extracellular complex. The 3D refinement was applied with C2 symmetry PDB-6q2s: Cryo-EM structure of RET/GFRa3/ARTN extracellular complex. The 3D refinement was applied with C2 symmetry. Method: EM (single particle) / Resolution: 3.8 Å EMDB-20580: Cryo-EM structure of RET/GFRa3/ARTN extracellular complex. The 3D refinement was focused on one of two halves with C1 symmetry applied. Method: EM (single particle) / Resolution: 3.5 Å
Chemicals	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose ChemComp-CA: Unknown entry
Source	homo sapiens (human) saccharomyces cerevisiae (brewer's yeast)
Keywords	SIGNALING PROTEIN / RET / receptor tyrosine kinase / cryo-EM