2hgf
HAIRPIN LOOP CONTAINING DOMAIN OF HEPATOCYTE GROWTH FACTOR, NMR, MINIMIZED AVERAGE STRUCTURE
OverviewOverview
BACKGROUND: Hepatocyte growth factor (HGF) is a multipotent growth factor that transduces a wide range of biological signals, including mitogenesis, motogenesis, and morphogenesis. The N-terminal (N) domain of HGF, containing a hairpin-loop region, is important for receptor binding and the potent biological activities of HGF. The N domain is also the primary binding site for heparin or heparan sulfate, which enhances, receptor/ligand oligomerization and modulates receptor-dependent mitogenesis. The rational design of artificial modulators of HGF signaling requires a detailed understanding of the structures of HGF and its receptor, as well as the role of heparin proteoglycan; this study represents the first step towards that goal. RESULTS: We report here a high-resolution structure of the N domain of HGF. This first structure of HGF reveals a novel folding topology with a distinct pattern of charge distribution and indicates a possible heparin-binding site. CONCLUSIONS: The hairpin-loop region of the N domain plays a major role in stabilizing the structure and contributes to a putative heparin-binding site, which explains why it is required for biological functions. These results suggest several basic and/or polar residues that may be important for use in further mutational studies of heparin binding.
About this StructureAbout this Structure
2HGF is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
The solution structure of the N-terminal domain of hepatocyte growth factor reveals a potential heparin-binding site., Zhou H, Mazzulla MJ, Kaufman JD, Stahl SJ, Wingfield PT, Rubin JS, Bottaro DP, Byrd RA, Structure. 1998 Jan 15;6(1):109-16. PMID:9493272 Page seeded by OCA on Sun May 4 06:15:41 2008