2hgf
From Proteopedia
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==Overview== | ==Overview== | ||
| - | BACKGROUND: Hepatocyte growth factor (HGF) is a multipotent growth factor | + | 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. |
==Disease== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Bottaro, D | + | [[Category: Bottaro, D P.]] |
| - | [[Category: Byrd, R | + | [[Category: Byrd, R A.]] |
| - | [[Category: Kaufman, J | + | [[Category: Kaufman, J D.]] |
| - | [[Category: Mazzulla, M | + | [[Category: Mazzulla, M J.]] |
| - | [[Category: Rubin, J | + | [[Category: Rubin, J S.]] |
| - | [[Category: Stahl, S | + | [[Category: Stahl, S J.]] |
| - | [[Category: Wingfield, P | + | [[Category: Wingfield, P T.]] |
[[Category: Zhou, H.]] | [[Category: Zhou, H.]] | ||
[[Category: hairpin loop]] | [[Category: hairpin loop]] | ||
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[[Category: scatter factor]] | [[Category: scatter factor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:41:39 2008'' |
Revision as of 15:41, 21 February 2008
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HAIRPIN LOOP CONTAINING DOMAIN OF HEPATOCYTE GROWTH FACTOR, NMR, MINIMIZED AVERAGE STRUCTURE
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Fibromatosis, gingival OMIM:[182530], Noonan syndrome 4 OMIM:[182530]
About this Structure
2HGF is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Thu Feb 21 17:41:39 2008
