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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)


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
Issue number11
Publication statusPublished - 2003 Mar 25
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry


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