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Structural characterization of CAS SH3 domain selectivity and regulation reveals new CAS interaction partners
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SYSNO ASEP 0478474 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Structural characterization of CAS SH3 domain selectivity and regulation reveals new CAS interaction partners Author(s) Gemperle, J. (CZ)
Hexnerová, Rozálie (UOCHB-X) ORCID, RID
Lepšík, Martin (UOCHB-X) RID, ORCID
Těšina, Petr (UOCHB-X)
Dibus, M. (CZ)
Novotný, M. (CZ)
Brábek, J. (CZ)
Veverka, Václav (UOCHB-X) RID, ORCID
Rösel, D. (CZ)Article number 8057 Source Title Scientific Reports. - : Nature Publishing Group - ISSN 2045-2322
Roč. 7, Aug 14 (2017)Number of pages 18 s. Language eng - English Country GB - United Kingdom Keywords focal adhesion kinase ; Src-transformed cells ; tyrosine phosphorylation Subject RIV CE - Biochemistry OECD category Biochemistry and molecular biology R&D Projects GBP208/12/G016 GA ČR - Czech Science Foundation (CSF) LO1304 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UOCHB-X - RVO:61388963 UT WOS 000407559800024 EID SCOPUS 85027462937 DOI 10.1038/s41598-017-08303-4 Annotation CAS is a docking protein downstream of the proto-oncogene Src with a role in invasion and metastasis of cancer cells. The CAS SH3 domain is indispensable for CAS-mediated signaling, but structural aspects of CAS SH3 ligand binding and regulation are not well understood. Here, we identified the consensus CAS SH3 binding motif and structurally characterized the CAS SH3 domain in complex with ligand. We revealed the requirement for an uncommon centrally localized lysine residue at position +2 of CAS SH3 ligands and two rather dissimilar optional anchoring residues, leucine and arginine, at position +5. We further expanded the knowledge of CAS SH3 ligand binding regulation by manipulating tyrosine 12 phosphorylation and confirmed the negative role of this phosphorylation on CAS SH3 ligand binding. Finally, by exploiting the newly identified binding requirements of the CAS SH3 domain, we predicted and experimentally verified two novel CAS SH3 binding partners, DOK7 and GLIS2. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434 Year of Publishing 2018 Electronic address https://www.nature.com/articles/s41598-017-08303-4
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