5G1D

The complex structure of syntenin-1 PDZ domain with c-terminal extension

5G1D の概要

• エントリーDOI: 10.2210/pdb5g1d/pdb
• 関連するPDBエントリー: 5G1E
• 分子名称: SYNTENIN-1, SYNDECAN-4 (2 entities in total)
• 機能のキーワード: signaling protein
• 由来する生物種: RATTUS NORVEGICUS (NORWAY RAT); 詳細
• 細胞内の位置: Cell junction, focal adhesion : Q9JI92
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 45472.51

構造登録者

Lee, I.,Kim, H.,Yun, J.H.,Lee, W. (登録日: 2016-03-25, 公開日: 2016-11-23, 最終更新日: 2024-05-08)

主引用文献

Choi, Y.,Yun, J.H.,Yoo, J.,Kim, H.,Lee, I.,Son, H.N.,Kim, I.S.,Yoon, H.S.,Zimmermann, P.,Couchman, J.R.,Cho, H.S.,Oh, E.S.,Lee, W.
New Structural Insight of C-Terminal Region of Syntenin-1, Enhancing the Molecular Dimerization and Inhibitory Function Related on Syndecan-4 Signaling.
Sci.Rep., 6:36818-, 2016

PubMed Abstract: 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.

PubMed: 27830760
DOI: 10.1038/SREP36818

実験手法

X-RAY DIFFRACTION (2.81 Å)