7moa | pdb_00007moa

Cryo-EM structure of the c-MET II/HGF I complex bound with HGF II in a rigid conformation

spinqualitylabelsall models 7moa, resolution 4.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7moa is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.9Å Ligands: IDS, SGN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease HGF_HUMAN Defects in HGF are the cause of deafness autosomal recessive type 39 (DFNB39) [MIM:608265. A form of profound prelingual sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. Function HGF_HUMAN Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types. Activating ligand for the receptor tyrosine kinase MET by binding to it and promoting its dimerization. Publication Abstract from PubMed The c-MET receptor is a receptor tyrosine kinase (RTK) that plays essential roles in normal cell development and motility. Aberrant activation of c-MET can lead to both tumors growth and metastatic progression of cancer cells. C-MET can be activated by either hepatocyte growth factor (HGF), or its natural isoform NK1. Here, we report the cryo-EM structures of c-MET/HGF and c-MET/NK1 complexes in the active state. The c-MET/HGF complex structure reveals that, by utilizing two distinct interfaces, one HGF molecule is sufficient to induce a specific dimerization mode of c-MET for receptor activation. The binding of heparin as well as a second HGF to the 2:1 c-MET:HGF complex further stabilize this active conformation. Distinct to HGF, NK1 forms a stable dimer, and bridges two c-METs in a symmetrical manner for activation. Collectively, our studies provide structural insights into the activation mechanisms of c-MET, and reveal how two isoforms of the same ligand use dramatically different mechanisms to activate the receptor. Structural basis of the activation of c-MET receptor.,Uchikawa E, Chen Z, Xiao GY, Zhang X, Bai XC Nat Commun. 2021 Jul 1;12(1):4074. doi: 10.1038/s41467-021-24367-3. PMID:34210960 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Hepatocyte growth factor Hepatocyte growth factor receptor 3D structures

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