Dual-site recognition of different extracellular matrix components by anti-angiogenic/neurotrophic serpin, PEDF

Norihisa Yasui, Terumi Mori, Daisuke Morito, Osamu Matsushita, Hiroki Kourai, Kazuhiro Nagata, Takaki Koide*

*この研究の対応する著者

研究成果: Article査読

63 被引用数 (Scopus)

抄録

Pigment epithelium-derived factor (PEDF), a member of the serine protease inhibitor (serpin) superfamily, possesses anti-angiogenic and neurotrophic activities. PEDF has been reported to bind to extracellular matrix (ECM) components such as collagens and glycosaminoglycans (GAGs). In this study, to determine the binding sites for collagens and GAGs, we analyzed the interaction of recombinant mouse PEDF (rPEDF) with collagen I and heparin. By utilizing residue-specific chemical modification and site-directed mutagenesis techniques, we revealed that the acidic amino acid residues on PEDF (Asp255, Asp257, and Asp299) are critical to collagen binding, and three clustered basic amino acid residues (Arg145, Lys146, and Arg148) are necessary for heparin binding. Mapping of these residues on the crystal structure of human PEDF (Simonovic, M., Gettins, P. G. W., and Volz, K. (2001) Proc. Natl. Acad. Sci. U.S.A. 98, 11131-11135) demonstrated that the collagen-binding site is oriented toward the opposite side of the highly basic surface where the heparin-binding site is localized. These results indicate that PEDF possesses dual binding sites for different ECM components, and this unique localization of ECM-binding sites implies that the binding to ECM components could regulate PEDF activities.

本文言語English
ページ(範囲)3160-3167
ページ数8
ジャーナルBiochemistry
42
11
DOI
出版ステータスPublished - 2003 3月 25
外部発表はい

ASJC Scopus subject areas

  • 生化学

フィンガープリント

「Dual-site recognition of different extracellular matrix components by anti-angiogenic/neurotrophic serpin, PEDF」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル