2ASU

Crystal Structure of the beta-chain of HGFl/MSP

2ASU の概要

• エントリーDOI: 10.2210/pdb2asu/pdb
• 関連するPDBエントリー: 1BUI
• 分子名称: Hepatocyte growth factor-like protein (3 entities in total)
• 機能のキーワード: serine proteinase, beta-chain, msp, hgfl, hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted: P26927 P26927
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28354.75

構造登録者

Carafoli, F.,Chirgadze, D.Y.,Blundell, T.L.,Gherardi, E. (登録日: 2005-08-24, 公開日: 2005-11-10, 最終更新日: 2024-11-06)

主引用文献

Carafoli, F.,Chirgadze, D.Y.,Blundell, T.L.,Gherardi, E.
Crystal structure of the beta-chain of human hepatocyte growth factor-like/macrophage stimulating protein.
Febs J., 272:5799-5807, 2005

PubMed Abstract: 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.

PubMed: 16279944
DOI: 10.1111/j.1742-4658.2005.04968.x

実験手法

X-RAY DIFFRACTION (1.85 Å)