title: PDZ tandem of human syntenin: crystal structure and functional properties.
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.
authors.affiliation: Department of Molecular Physiology and Biological Physics and The Cancer Center, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Beom Sik
authors.initials: BS
authors.lastname: Kang
authors.forename: David R
authors.initials: DR
authors.lastname: Cooper
authors.forename: Filip
authors.initials: F
authors.lastname: Jelen
authors.forename: Yancho
authors.initials: Y
authors.lastname: Devedjiev
authors.forename: Urszula
authors.initials: U
authors.lastname: Derewenda
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Dauter
authors.forename: Jacek
authors.initials: J
authors.lastname: Otlewski
authors.forename: Zygmunt S
authors.initials: ZS
authors.lastname: Derewenda
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D025581:Neurofibromin 2 / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000378:metabolism; D016415:Sequence Alignment; D053667:Syndecans; D053676:Syntenins
chemical_list: D000199:Actins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D025581:Neurofibromin 2; D010446:Peptide Fragments; D011509:Proteoglycans; C109621:SDCBP protein, human; D053667:Syndecans; D053676:Syntenins