1nk1
From Proteopedia
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| , resolution 2.50Å | |||||||
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| Gene: | HEPATOCYTE GROWTH FACTOR/SCATTER FACTOR (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
NK1 FRAGMENT OF HUMAN HEPATOCYTE GROWTH FACTOR/SCATTER FACTOR (HGF/SF) AT 2.5 ANGSTROM RESOLUTION
Contents |
Overview
Although ligand-induced receptor dimerization is a common prerequisite for receptor activation, the mode by which different growth factors bind their receptors and cause them to dimerize varies considerably. Here we report the crystal structure at 2.5 A resolution of NK1, a receptor-binding fragment and a natural splice variant of hepatocyte growth factor/scatter factor (HGF/SF). NK1 assembles as a homodimer in the asymmetric unit, revealing a novel mode of growth factor dimerization produced by close packing of the N domain of one subunit and the kringle domain of the other, thus bringing the two linkers in close proximity. The structure suggests the presence of a binding site for heparan sulfate chains and a mechanism by which the NK1 dimer may engage two receptor molecules through clusters of amino acids located on each protomer and on opposite surfaces of the homodimer. We also report that short (14-mer) heparin fragments effectively dimerize NK1 in solution, implying that heparan sulfate chains may stabilize the NK1 dimer. These results provide a basis for the agonistic activity of NK1 and have implications for the mechanism of receptor binding of HGF/SF.
Disease
Known diseases associated with this structure: Fibromatosis, gingival OMIM:[182530], Noonan syndrome 4 OMIM:[182530]
About this Structure
1NK1 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the NK1 fragment of HGF/SF suggests a novel mode for growth factor dimerization and receptor binding., Chirgadze DY, Hepple JP, Zhou H, Byrd RA, Blundell TL, Gherardi E, Nat Struct Biol. 1999 Jan;6(1):72-9. PMID:9886295
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