PEDF and the serpins: Phylogeny, sequence conservation, and functional domains

Joyce Tombran-Tink, Samuel Aparicio, Xuming Xu, Amber R. Tink, Nuria Lara, Supriya Sawant, Colin J. Barnstable, Samuel Shao Min Zhang

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Pigment epithelium derived factor (PEDF) is non-inhibitory serpin with neurotrophic and antiangiogenic functions. In this study, we have assembled PEDF sequences for 9 additional species by data base mining and performed cross-species alignment for 14 PEDF sequences to identify conserved structural domains. We found evolutionary conservation of a leader sequence, a single C-terminal glycosylation site, collagen-binding residues, and four specific conserved PEDF peptides. The C-terminus, 384-415 and an N-terminal region 78-95, show close homology with many other serpins, and there is strong conservation of 39 of 51 consensus key residues involved in serpin structure and function. Two peptide regions, 40-67 and 277-301, are unique to PEDF but conserved in all species. Conserved residues at the N-terminus, helix d (hD), and helix A (hA) of PEDF form a structure similar to the heparin-binding groove of other serpins. We identified a motif in PEDF that is homologous to the nuclear localization signals of other proteins. A bitopographical localization of PEDF was confirmed by immunocytochemistry and Western blots. Our results suggest that secretion is required for PEDF's activity, that PEDF can migrate to the nucleus, and that PEDF has structural and functional features more common with inhibitory serpins.

Original languageEnglish (US)
Pages (from-to)130-150
Number of pages21
JournalJournal of Structural Biology
Volume151
Issue number2
DOIs
StatePublished - Aug 1 2005

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Serpins
Phylogeny
pigment epithelium-derived factor
Nuclear Localization Signals
Peptides
Data Mining
Glycosylation
Heparin
Collagen
Western Blotting
Immunohistochemistry
Binding Sites
Databases

All Science Journal Classification (ASJC) codes

  • Structural Biology

Cite this

Tombran-Tink, Joyce ; Aparicio, Samuel ; Xu, Xuming ; Tink, Amber R. ; Lara, Nuria ; Sawant, Supriya ; Barnstable, Colin J. ; Zhang, Samuel Shao Min. / PEDF and the serpins : Phylogeny, sequence conservation, and functional domains. In: Journal of Structural Biology. 2005 ; Vol. 151, No. 2. pp. 130-150.
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PEDF and the serpins : Phylogeny, sequence conservation, and functional domains. / Tombran-Tink, Joyce; Aparicio, Samuel; Xu, Xuming; Tink, Amber R.; Lara, Nuria; Sawant, Supriya; Barnstable, Colin J.; Zhang, Samuel Shao Min.

In: Journal of Structural Biology, Vol. 151, No. 2, 01.08.2005, p. 130-150.

Research output: Contribution to journalArticle

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