1NK1

NK1 FRAGMENT OF HUMAN HEPATOCYTE GROWTH FACTOR/SCATTER FACTOR (HGF/SF) AT 2.5 ANGSTROM RESOLUTION

1NK1 の概要

• エントリーDOI: 10.2210/pdb1nk1/pdb
• 分子名称: PROTEIN (HEPATOCYTE GROWTH FACTOR PRECURSOR) (2 entities in total)
• 機能のキーワード: hgf/sf, hormone-growth factor complex, hormone/growth factor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 42344.55

構造登録者

Chirgadze, D.Y.,Hepple, J.P.,Zhou, H.,Byrd, R.A.,Blundell, T.L.,Gherardi, E. (登録日: 1998-08-20, 公開日: 1999-01-13, 最終更新日: 2024-11-06)

主引用文献

Chirgadze, D.Y.,Hepple, J.P.,Zhou, H.,Byrd, R.A.,Blundell, T.L.,Gherardi, E.
Crystal structure of the NK1 fragment of HGF/SF suggests a novel mode for growth factor dimerization and receptor binding.
Nat.Struct.Biol., 6:72-79, 1999

PubMed Abstract: 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.

PubMed: 9886295
DOI: 10.1038/4947

実験手法

X-RAY DIFFRACTION (2.5 Å)