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PEDF and the serpins: phylogeny, sequence conservation, and functional domains
Joyce Tombran-Tink1, Samuel Aparicio, Xuming Xu
1Division of Pharmaceutical Sciences, University of Missouri-Kansas City, Kansas City, MO 64110, USA. jttink@aol.com
Journal of Structural Biology
|July 26, 2005
Summary
Pigment epithelium derived factor (PEDF) is a neurotrophic protein. Cross-species analysis reveals conserved regions, suggesting shared functions with inhibitory serpins and nuclear migration capabilities.
Area of Science:
- Molecular Biology
- Evolutionary Biology
- Biochemistry
Background:
- Pigment epithelium derived factor (PEDF) is a secreted protein known for its neurotrophic and antiangiogenic properties.
- PEDF belongs to the serpin superfamily but lacks inhibitory function.
Purpose of the Study:
- To identify conserved structural domains and evolutionary features of PEDF across multiple species.
- To compare PEDF's structure and function with other serpins.
Main Methods:
- Database mining to assemble PEDF sequences from 9 additional species.
- Cross-species sequence alignment of 14 PEDF sequences.
- Identification of conserved residues, peptides, and motifs.
- Immunocytochemistry and Western blots for protein localization.
Main Results:
- Evolutionary conservation of a leader sequence, C-terminal glycosylation site, collagen-binding residues, and unique PEDF peptides (40-67, 277-301).
- Homology between PEDF's N-terminus, helix d, and helix A with heparin-binding grooves of other serpins.
- Identification of a nuclear localization signal-like motif in PEDF.
- Confirmation of PEDF secretion and nuclear migration via immunocytochemistry and Western blots.
Conclusions:
- PEDF possesses conserved structural elements, including unique regions and domains homologous to inhibitory serpins.
- Secretion is essential for PEDF activity, and it can translocate to the nucleus.
- PEDF shares structural and functional characteristics with inhibitory serpins, despite its non-inhibitory nature.