Hepatocyte growth factor

From Proteopedia

Function Hepatocyte growth factor (HGF) regulates cell growth, motility and morphogenesis. HGF binds to proto-oncogene c-Met receptor and activates a tyrosine kinase signaling cascade. HGF precursor is cleaved by serine protease to α (69 kD) and β (34 kD) chains which form a disulfide bond to produce the active heterodimer[1]. HGF α chain contains an N-terminal hairpin and 4 kringle domains. The kringle domain participates in protein-protein interaction and its structure is of a large loop which is stabilized by 3 Cys-Cys bonds. HGF β chain is catalytically inactive serine protease-like. HGF NK1 - a natural splice variant is comprised of residues 28-210 containing the N-terminus and the first kringle domain of HGF[2]. HGF NK2 variant is comprised of residues 28-289 containing the N-terminus and the first 2 kringle domains of HGF. See also Hepatocyte growth factor receptor. Relevance High levels of HGF are associated with liver diseases[3], lung diseases, acute cardiac infraction, vascular diseases, renal failure, neurologic diseases like Alzheimer Disease, pancreatic diseases, several types of cancer and diabetes type II[4][5]. HGF administration can reverse liver chirrosis[6].

spinqualitylabelsall models Structure of human HGF β chain (grey) complex with HGF receptor Sema and ψ domains (green) (PDB entry 1shy) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

3D structures of hepatocyte growth factor

Updated on 16-May-2023

HGF full length 1-728

7mo7, 7mo8, 7mo9, 7moa, 7mob – hHGF + hHGFR – human – Cryo EM

HGF N terminal 28-126

2hgf – hHGF N terminal – human - NMR

3hms, 3hmt – hHGF N terminal

3hmr – mHGF N terminal – mouse

HGF NK1 variant 28-210

1bht, 1nk1, 1gp9, 2qj2, 2qj4 – hHGF NK1

5cs1, 5cs5, 5cs9, 5coe – hHGF NK1 (mutant)

1gmn, 1gmo, 3mkp – hHGF NK1 (mutant) + heparin

5ct1, 5ct2, 5ct3, 5cs3, 5csq, 5cp9 – hHGF NK1 (mutant) + inhibitor

4d3c – hHGF NK1 (mutant) + antibody

HGF NK2 variant 28-289

3hn4 – hHGF NK2

3sp8 – hHGF NK2 (mutant) + heparin

4iua – mHGF NK2 (mutant)

HGF α chain (69 kD) 495-728

1si5 – hHGF α chain (mutant)

1shy – hHGF α chain (mutant) + HGF receptor Sema and ψ domains

HGF β chain 25-567

4o3t, 4o3u – hHGF β chain (mutant) + HGF receptor Sema and ψ domains + zymogen activator peptide

HGF α+β chain

4k3j – hHGF α (mutant) + β + antibody

6lz9 – hHGF α (mutant) + K4 domain 388-494 + antibody

References

1. ↑ Nakamura T. Structure and function of hepatocyte growth factor. Prog Growth Factor Res. 1991;3(1):67-85. PMID:1838014
2. ↑ Jakubczak JL, LaRochelle WJ, Merlino G. NK1, a natural splice variant of hepatocyte growth factor/scatter factor, is a partial agonist in vivo. Mol Cell Biol. 1998 Mar;18(3):1275-83. PMID:9488442
3. ↑ Shiota G, Okano J, Kawasaki H, Kawamoto T, Nakamura T. Serum hepatocyte growth factor levels in liver diseases: clinical implications. Hepatology. 1995 Jan;21(1):106-12. PMID:7806142
4. ↑ Anan F, Masaki T, Yonemochi H, Takahashi N, Nakagawa M, Eshima N, Saikawa T, Yoshimatsu H. Hepatocyte growth factor levels are associated with the results of 123I-metaiodobenzylguanidine myocardial scintigraphy in patients with type 2 diabetes mellitus. Metabolism. 2009 Feb;58(2):167-73. doi: 10.1016/j.metabol.2008.09.009. PMID:19154948 doi:http://dx.doi.org/10.1016/j.metabol.2008.09.009
5. ↑ Shiota G, Okano J, Kawasaki H, Kawamoto T, Nakamura T. Serum hepatocyte growth factor levels in liver diseases: clinical implications. Hepatology. 1995 Jan;21(1):106-12. PMID:7806142
6. ↑ Funakoshi H, Nakamura T. Hepatocyte growth factor: from diagnosis to clinical applications. Clin Chim Acta. 2003 Jan;327(1-2):1-23. PMID:12482615