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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Youngsil Choi
  • Ji-Hye Yun
  • Jiho Yoo
  • Inhwan Lee
  • Heeyoun Kim
  • Hye-Nam Son
  • In-San Kim
  • Ho Sup Yoon
  • Pascale Zimmermann
  • Couchman, John Robert
  • Hyun-Soo Cho
  • Eok-Soo Oh
  • Weontae Lee

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.

Original languageEnglish
Article number36818
JournalScientific Reports
Number of pages16
Publication statusPublished - 10 Nov 2016

ID: 169361018