2asu
From Proteopedia
(New page: 200px<br /> <applet load="2asu" size="450" color="white" frame="true" align="right" spinBox="true" caption="2asu, resolution 1.85Å" /> '''Crystal Structure o...) |
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| - | [[Image:2asu.gif|left|200px]]<br /> | + | [[Image:2asu.gif|left|200px]]<br /><applet load="2asu" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2asu, resolution 1.85Å" /> | caption="2asu, resolution 1.85Å" /> | ||
'''Crystal Structure of the beta-chain of HGFl/MSP'''<br /> | '''Crystal Structure of the beta-chain of HGFl/MSP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Hepatocyte growth factor like/macrophage stimulating protein (HGFl/MSP) | + | Hepatocyte growth factor like/macrophage stimulating protein (HGFl/MSP) and hepatocyte growth factor/scatter factor (HGF/SF) define a distinct family of vertebrate-specific growth factors structurally related to the blood proteinase precursor plasminogen and with important roles in development and cancer. Although the two proteins share a similar domain structure and mechanism of activation, there are differences between HGFl/MSP and HGF/SF in terms of the contribution of individual domains to receptor binding. Here we present a crystal structure of the 30 kDa beta-chain of human HGFl/MSP, a serine proteinase homology domain containing the high-affinity binding site for the RON receptor. The structure describes at 1.85 Angstrom resolution the region of the domain corresponding to the receptor binding site recently defined in the HGF/SF beta-chain, namely the central cleft harboring the three residues corresponding to the catalytic ones of active proteinases (numbers in brackets define the sequence position according to the standard chymotrypsinogen numbering system) [Gln522 (c57), Gln568 (c102) and Tyr661 (c195)] and an adjacent loop flanking the S1 specificity pocket and containing residues Asn682 (c217) and Arg683 (c218) previously shown to be essential for binding of HGFl/MSP to the RON receptor. The study confirms the concept that the serine proteinase homology domains of HGFl/MSP and HGF/SF bind their receptors in an 'enzyme-substrate' mode, reflecting the common evolutionary origin of the plasminogen-related growth factors and the proteinases of the clotting and fibrinolytic pathways. However, analysis of the intermolecular interactions in the crystal lattice of beta-chain HGFl/MSP fails to show the same contacts seen in the HGF/SF structures and does not support a conserved mode of dimerization of the serine proteinase homology domains of HGFl/MSP and HGF/SF responsible for receptor activation. |
==About this Structure== | ==About this Structure== | ||
| - | 2ASU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 2ASU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ASU OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Blundell, T | + | [[Category: Blundell, T L.]] |
[[Category: Carafoli, F.]] | [[Category: Carafoli, F.]] | ||
| - | [[Category: Chirgadze, D | + | [[Category: Chirgadze, D Y.]] |
[[Category: Gherardi, E.]] | [[Category: Gherardi, E.]] | ||
[[Category: beta-chain]] | [[Category: beta-chain]] | ||
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[[Category: serine proteinase]] | [[Category: serine proteinase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:30:41 2008'' |
Revision as of 14:30, 21 February 2008
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Crystal Structure of the beta-chain of HGFl/MSP
Overview
Hepatocyte growth factor like/macrophage stimulating protein (HGFl/MSP) and hepatocyte growth factor/scatter factor (HGF/SF) define a distinct family of vertebrate-specific growth factors structurally related to the blood proteinase precursor plasminogen and with important roles in development and cancer. Although the two proteins share a similar domain structure and mechanism of activation, there are differences between HGFl/MSP and HGF/SF in terms of the contribution of individual domains to receptor binding. Here we present a crystal structure of the 30 kDa beta-chain of human HGFl/MSP, a serine proteinase homology domain containing the high-affinity binding site for the RON receptor. The structure describes at 1.85 Angstrom resolution the region of the domain corresponding to the receptor binding site recently defined in the HGF/SF beta-chain, namely the central cleft harboring the three residues corresponding to the catalytic ones of active proteinases (numbers in brackets define the sequence position according to the standard chymotrypsinogen numbering system) [Gln522 (c57), Gln568 (c102) and Tyr661 (c195)] and an adjacent loop flanking the S1 specificity pocket and containing residues Asn682 (c217) and Arg683 (c218) previously shown to be essential for binding of HGFl/MSP to the RON receptor. The study confirms the concept that the serine proteinase homology domains of HGFl/MSP and HGF/SF bind their receptors in an 'enzyme-substrate' mode, reflecting the common evolutionary origin of the plasminogen-related growth factors and the proteinases of the clotting and fibrinolytic pathways. However, analysis of the intermolecular interactions in the crystal lattice of beta-chain HGFl/MSP fails to show the same contacts seen in the HGF/SF structures and does not support a conserved mode of dimerization of the serine proteinase homology domains of HGFl/MSP and HGF/SF responsible for receptor activation.
About this Structure
2ASU is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the beta-chain of human hepatocyte growth factor-like/macrophage stimulating protein., Carafoli F, Chirgadze DY, Blundell TL, Gherardi E, FEBS J. 2005 Nov;272(22):5799-807. PMID:16279944
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