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

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3160-3167
Number of pages8
JournalBiochemistry
Volume42
Issue number11
DOIs
Publication statusPublished - Mar 25 2003
Externally publishedYes

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Serine Proteinase Inhibitors
Extracellular Matrix
Collagen
Binding Sites
Heparin
Glycosaminoglycans
Acidic Amino Acids
Basic Amino Acids
Mutagenesis
Chemical modification
Site-Directed Mutagenesis
pigment epithelium-derived factor
Crystal structure

ASJC Scopus subject areas

  • Biochemistry

Cite this

Dual-site recognition of different extracellular matrix components by anti-angiogenic/neurotrophic serpin, PEDF. / Yasui, Norihisa; Mori, Terumi; Morito, Daisuke; Matsushita, Osamu; Kourai, Hiroki; Nagata, Kazuhiro; Koide, Takaki.

In: Biochemistry, Vol. 42, No. 11, 25.03.2003, p. 3160-3167.

Research output: Contribution to journalArticle

Yasui, Norihisa ; Mori, Terumi ; Morito, Daisuke ; Matsushita, Osamu ; Kourai, Hiroki ; Nagata, Kazuhiro ; Koide, Takaki. / Dual-site recognition of different extracellular matrix components by anti-angiogenic/neurotrophic serpin, PEDF. In: Biochemistry. 2003 ; Vol. 42, No. 11. pp. 3160-3167.
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