Tyrosine 51 residue of the syndecan-2 extracellular domain is involved in the interaction with and activation of pro-matrix metalloproteinase-7

Bohee Jang, Ji Hye Yun, Sojoong Choi, Jimin Park, Dong Hae Shin, Seung Taek Lee, Weontae Lee, Eok Soo Oh

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Abstract

Although syndecan-2 is known to interact with the matrix metalloproteinase-7 (MMP-7), the details of their interaction were unknown. Our experiments with a series of syndecan-2 extracellular domain deletion mutants show that the interaction is mediated through an interaction of the extracellular domain of syndecan-2 (residues 41 to 60) with the α2 helix-loop-α3 helix in the pro-domain of MMP-7. NMR and molecular docking model show that Glu7 of the α1 helix, Glu32 of the α2 helix, and Gly48 and Ser52 of the α2 helix-loop-α3 helix of the MMP-7 pro-domain form the syndecan-2-binding pocket, which is occupied by the side chain of tyrosine residue 51 (Tyr51) of syndecan-2. Consistent with this notion, the expression of a syndecan-2 mutant in which Tyr51 was changed to Ala diminished the interaction between the syndecan-2 extracellular domain and the pro-domain of MMP-7. Furthermore, HT-29 colon adenocarcinoma cells expressing the interaction-defective mutant exhibited reductions in the cell-surface localization of MMP-7, the processing of pro-MMP-7 into active MMP-7, the MMP-7-mediated extracellular domain shedding of both syndecan-2 and E-cadherin, and syndecan-2-mediated anchorage-independent growth. Collectively, these data strongly suggest that Tyr51 of the syndecan-2 extracellular domain mediates its interaction with and activating processing of pro-MMP-7 and regulates MMP-7-dependent syndecan-2 functions.

Original languageEnglish
Article number10625
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

Bibliographical note

Funding Information:
This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2017R1A2B4008680) and the Ministry of Trade, Industry & Energy (MOTIE), Korea Institute for Advancement of Technology (KIAT) through the Encouragement Program for The Industries of Economic Cooperation Region (R0006245) and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2019R1A2C2009011). This work was supported by NRF-2017R1A2B2008483 to WL and the Basic Science Research Program (NRF-2016R1A6A3A04010213 to JHY) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education.

Publisher Copyright:
© 2019, The Author(s).

All Science Journal Classification (ASJC) codes

  • General

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