Abstract |
Syntenin, a 33 kDa protein, interacts with several cell membrane receptors and with merlin, the product of the causal gene for neurofibromatosis type II. We report a crystal structure of the functional fragment of human syntenin containing two canonical PDZ domains, as well as binding studies for full-length syntenin, the PDZ tandem, and isolated PDZ domains. We show that the functional properties of syntenin are a result of independent interactions with target peptides, and that each domain is able to bind peptides belonging to two different classes: PDZ1 binds peptides from classes I and III, while PDZ2 interacts with classes I and II. The independent binding of merlin by PDZ1 and syndecan-4 by PDZ2 provides direct evidence for the coupling of syndecan-mediated signaling to actin regulation by merlin.
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Authors | Beom Sik Kang, David R Cooper, Filip Jelen, Yancho Devedjiev, Urszula Derewenda, Zbigniew Dauter, Jacek Otlewski, Zygmunt S Derewenda |
Journal | Structure (London, England : 1993)
(Structure)
Vol. 11
Issue 4
Pg. 459-68
(Apr 2003)
ISSN: 0969-2126 [Print] United States |
PMID | 12679023
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Actins
- Carrier Proteins
- Intracellular Signaling Peptides and Proteins
- Membrane Glycoproteins
- Membrane Proteins
- Neurofibromin 2
- Peptide Fragments
- Proteoglycans
- SDCBP protein, human
- Syndecans
- Syntenins
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Topics |
- Actins
(metabolism)
- Amino Acid Sequence
- Animals
- Carrier Proteins
(chemistry, genetics, metabolism)
- Crystallography, X-Ray
- Cytoskeleton
(metabolism)
- Humans
- Intracellular Signaling Peptides and Proteins
- Membrane Glycoproteins
(metabolism)
- Membrane Proteins
(chemistry, genetics, metabolism)
- Models, Molecular
- Molecular Sequence Data
- Neurofibromin 2
(chemistry, metabolism)
- Peptide Fragments
(chemistry, genetics, metabolism)
- Protein Binding
- Protein Structure, Tertiary
- Proteoglycans
(metabolism)
- Sequence Alignment
- Syndecans
- Syntenins
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