Choi, Youngsil Yun, Ji-Hye Yoo, Jiho Lee, Inhwan Kim, Heeyoun Son, Hye-Nam Kim, In-San Yoon, Ho Sup Zimmermann, Pascale Couchman, John R. Cho, Hyun-Soo Oh, Eok-Soo Lee, Weontae 2024-01-20T03:01:30Z 2024-01-20T03:01:30Z 2021-09-05 2016-11-10 2045-2322 https://pubs.kist.re.kr/handle/201004/123441 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. English NATURE PUBLISHING GROUP CYTOPLASMIC DOMAIN PDZ DOMAINS PROTEIN MIGRATION ORGANIZATION ACTIVATION ADHESION New structural insight of C-terminal region of Syntenin-1, enhancing the molecular dimerization and inhibitory function related on Syndecan-4 signaling Article 10.1038/srep36818 1 SCIENTIFIC REPORTS, v.6 SCIENTIFIC REPORTS 6 scie scopus 000387872800001 2-s2.0-84994868782 Multidisciplinary Sciences Science & Technology - Other Topics Article CYTOPLASMIC DOMAIN PDZ DOMAINS PROTEIN MIGRATION ORGANIZATION ACTIVATION ADHESION