The central region of testican-2 forms a compact core and promotes cell migration

Krajnc, Anja (author), Gaber, Aljaž (author), Lenarčič, Brigita (author), Pavšič, Miha (author)

Testicans are modular proteoglycans of the extracellular matrix of various tissues where they contribute to matrix integrity and exert cellular effects like neurite outgrowth and cell migration. Using testican-2 as a representative member of the family, we tackle the complete lack of general structural information and structure–function relationship. First, we show using isothermal titration calorimetry and modeling that extracellular calcium-binding domain (EC) has only one active calcium-binding site, while the other potential site is inactive, and that testican-2 is within extracellular matrix always in the calcium-loaded form. Next, we demonstrate using various prediction methods that N- and C-terminal regions plus interdomain connections are flexible. We support this by small-angle X-ray-scattering analysis of C-terminally truncated testican-2, which indicates that the triplet follistatin-EC-thyroglobulin domain forms a moderately compact core while the unique N-terminal is disordered. Finally, using cell exclusion zone assay, we show that it is this domain triplet that is responsible for promoting cell migration and not the N- and C-terminal regions.

• Language: English
• Keywords: testican, SPOCK, calcium-binding, structural model, cell migration
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: 17 str.
• Numbering: Vol. 21, iss. 24, art. 9413
• PID: 20.500.12556/RUL-134820
• UDC: 577.112.85
• ISSN on article: 1661-6596
• DOI: 10.3390/ijms21249413
• COBISS.SI-ID: 42261507
• Publication date in RUL: 03.02.2022

Record is a part of a journal

• Title: International journal of molecular sciences
• Shortened title: Int. j. mol. sci.
• Publisher: MDPI
• ISSN: 1661-6596
• COBISS.SI-ID: 36217605

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 10.12.2020

Secondary language

• Language: Slovenian
• Keywords: testikan, SPOCK, vezava kalcijevih ionov, model strukture, celična migracija

Projects

• Funder: ARRS - Slovenian Research Agency
• Funding programme: Young researchers