6q2s
Cryo-EM structure of RET/GFRa3/ARTN extracellular complex. The 3D refinement was applied with C2 symmetry.
Structural highlights
FunctionARTN_HUMAN Ligand for the GFR-alpha-3-RET receptor complex but can also activate the GFR-alpha-1-RET receptor complex. Supports the survival of sensory and sympathetic peripheral neurons in culture and also supports the survival of dopaminergic neurons of the ventral mid-brain. Strong attractant of gut hematopoietic cells thus promoting the formation Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue.[1] [2] SMT3_YEAST Not known; suppressor of MIF2 mutations. Publication Abstract from PubMedRET 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/GFRalpha1/RET, NRTN/GFRalpha2/RET and ARTN/GFRalpha3/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/GFRalpha2/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. 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 Elife. 2019 Sep 19;8. pii: 47650. doi: 10.7554/eLife.47650. PMID:31535977[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||
