View source for 7mo8


==Cryo-EM structure of 1:1 c-MET I/HGF I complex after focused 3D refinement of holo-complex==
<StructureSection load='7mo8' size='340' side='right'caption='[[7mo8]], [[Resolution|resolution]] 4.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7mo8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MO8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MO8 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IDS:2-O-SULFO-ALPHA-L-IDOPYRANURONIC+ACID'>IDS</scene>, <scene name='pdbligand=SGN:N,O6-DISULFO-GLUCOSAMINE'>SGN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7mo8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mo8 OCA], [https://pdbe.org/7mo8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mo8 RCSB], [https://www.ebi.ac.uk/pdbsum/7mo8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mo8 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/HGF_HUMAN HGF_HUMAN] Defects in HGF are the cause of deafness autosomal recessive type 39 (DFNB39) [MIM:[https://omim.org/entry/608265 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.<ref>PMID:19576567</ref> 
== Function ==
[https://www.uniprot.org/uniprot/HGF_HUMAN 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.<ref>PMID:15167892</ref> <ref>PMID:20624990</ref> 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:34210960</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7mo8" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hepatocyte growth factor|Hepatocyte growth factor]]
*[[Hepatocyte growth factor receptor 3D structures|Hepatocyte growth factor receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bai XC]]
[[Category: Chen ZM]]
[[Category: Uchikawa E]]
[[Category: Xiao GY]]
[[Category: Zhang XW]]