PDZ tandem of human syntenin: crystal structure and functional properties.
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.
Kang
Beom Sik
BS
Department of Molecular Physiology and Biological Physics and The Cancer Center, University of Virginia, Charlottesville, VA 22908, USA.
Cooper
David R
DR
Jelen
Filip
F
Devedjiev
Yancho
Y
Derewenda
Urszula
U
Dauter
Zbigniew
Z
Otlewski
Jacek
J
Derewenda
Zygmunt S
ZS
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
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