Send to

Choose Destination
Sci Rep. 2016 Nov 10;6:36818. doi: 10.1038/srep36818.

New structural insight of C-terminal region of Syntenin-1, enhancing the molecular dimerization and inhibitory function related on Syndecan-4 signaling.

Author information

Department of Life Sciences, Division of Life and Pharmaceutical Sciences and the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea.
Department of Biochemistry, College of Life Science &Biotechnology, Yonsei University, Seoul 120-749, Korea.
Department of Biology, College of Life Science &Biotechnology, Yonsei University, Seoul 136-791, Republic of Korea.
Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
Division of Structural and Computational Biology, School of Biological Sciences, Nanyang Technological University, Singapore.
Department of Genetic Engineering, College of Life Sciences, Kyung Hee University,Yongin-si Gyeonggi-do, 446-701, Republic of Korea.
Laboratory for Glycobiology, University of Leuven &Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium.
Department of Biomedical Sciences, University of Copenhagen, Biocenter, 2200 Copenhagen, Denmark.


The PDZ domain-containing scaffold protein, syntenin-1, binds to the transmembrane proteoglycan, syndecan-4, but the molecular mechanism/function of this interaction are unknown. Crystal structure analysis of syntenin-1/syndecan-4 cytoplasmic domains revealed that syntenin-1 forms a symmetrical pair of dimers anchored by a syndecan-4 dimer. The syndecan-4 cytoplasmic domain is a compact intertwined dimer with a symmetrical clamp shape and two antiparallel strands forming a cavity within the dimeric twist. The PDZ2 domain of syntenin-1 forms a direct antiparallel interaction with the syndecan-4 cytoplasmic domain, inhibiting the functions of syndecan-4 such as focal adhesion formation. Moreover, C-terminal region of syntenin-1 reveals an essential role for enhancing the molecular homodimerization. Mutation of key syntenin-1 residues involved in the syndecan-4 interaction or homodimer formation abolishes the inhibitory function of syntenin-1, as does deletion of the homodimerization-related syntenin-1 C-terminal domain. Syntenin-1, but not dimer-formation-incompetent mutants, rescued the syndecan-4-mediated inhibition of migration and pulmonary metastasis by B16F10 cells. Therefore, we conclude that syntenin-1 negatively regulates syndecan-4 function via oligomerization and/or syndecan-4 interaction, impacting cytoskeletal organization and cell migration.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center