HARNOŠ, Jakub, Jan RYNEŠ, Pavlína VÍŠKOVÁ, Silvie TRANTÍRKOVÁ, Lola Murielle BAJARD ÉP.ESNER, Lukáš TRANTÍREK and Vítězslav BRYJA. Analysis of binding interfaces of the human scaffold protein AXIN1 by peptide microarrays. Journal of Biological Chemistry. Bethesda, USA: Amer. Soc. Biochem. Mol. Biol., 2018, vol. 293, No 42, p. 16337-16347. ISSN 0021-9258. Available from: https://dx.doi.org/10.1074/jbc.RA118.005127.
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Basic information
Original name Analysis of binding interfaces of the human scaffold protein AXIN1 by peptide microarrays
Authors HARNOŠ, Jakub (203 Czech Republic, belonging to the institution), Jan RYNEŠ (203 Czech Republic, belonging to the institution), Pavlína VÍŠKOVÁ (203 Czech Republic, belonging to the institution), Silvie TRANTÍRKOVÁ (203 Czech Republic, belonging to the institution), Lola Murielle BAJARD ÉP.ESNER (250 France, belonging to the institution), Lukáš TRANTÍREK (203 Czech Republic, belonging to the institution) and Vítězslav BRYJA (203 Czech Republic, guarantor, belonging to the institution).
Edition Journal of Biological Chemistry, Bethesda, USA, Amer. Soc. Biochem. Mol. Biol. 2018, 0021-9258.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10608 Biochemistry and molecular biology
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 4.106
RIV identification code RIV/00216224:14310/18:00101698
Organization unit Faculty of Science
Doi http://dx.doi.org/10.1074/jbc.RA118.005127
UT WoS 000447833600018
Keywords in English peptide array; scaffold protein; axin; serine; threonine protein kinase; p53; Myc (c-Myc); casein kinase 1E; dishevelled; intrinsically disordered region; Wnt pathway
Tags rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Pavla Foltynová, Ph.D., učo 106624. Changed: 26/3/2019 13:07.
Abstract
Intrinsically disordered regions (IDRs) are protein regions that lack persistent secondary or tertiary structure under native conditions. IDRs represent >40% of the eukaryotic proteome and play a crucial role in protein-protein interactions. The classical approach for identification of these interaction interfaces is based on mutagenesis combined with biochemical techniques such as coimmunoprecipitation or yeast two-hybrid screening. This approach either provides information of low resolution (large deletions) or very laboriously tries to precisely define the binding epitope via single amino acid substitutions. Here, we report the use of a peptide microarray based on the human scaffold protein AXIN1 for high-throughput and -resolution mapping of binding sites for several AXIN1 interaction partners in vitro. For each of the AXIN1-binding partners tested, i.e. casein kinase 1 E (CK1E); c-Myc; peptidyl-prolyl cis/trans isomerase, NIMA-interacting 1 (Pin1); and p53, we found at least three different epitopes, predominantly in the central IDR of AXIN1. We functionally validated the specific AXIN1-CK1E interaction identified here with epitope-mimicking peptides and with AXIN1 variants having deletions of short binding epitopes. On the basis of these results, we propose a model in which AXIN1 competes with dishevelled (DVL) for CK1E and regulates CK1E-induced phosphorylation of DVL and activation of Wnt/-catenin signaling.
Links
GA17-12075S, research and development projectName: Polymorfní G-quadruplexy v promotorových oblastech genů
Investor: Czech Science Foundation
GA18-17658S, research and development projectName: Odhalení tajemství signální dráhy WNT analýzou struktury proteinu Dishevelled
Investor: Czech Science Foundation
GJ15-22380Y, research and development projectName: Molekulární stavba protein-DNA komplexů zapojených v opravě nukleotidových sestřihů
Investor: Czech Science Foundation
LQ1601, research and development projectName: CEITEC 2020 (Acronym: CEITEC2020)
Investor: Ministry of Education, Youth and Sports of the CR
MUNI/A/1145/2017, interní kód MUName: Podpora výzkumné činnosti studentů v oblasti fyziologie, vývojové biologie a imunologie živočichů v roce 2018 (Acronym: OFIŽ 2018)
Investor: Masaryk University, Category A
MUNI/G/1100/2016, interní kód MUName: Computational chemistry for Wnt signaling pathway
Investor: Masaryk University, INTERDISCIPLINARY - Interdisciplinary research projects
NV15-34405A, research and development projectName: Identifikace nových možností léčby chronické myeloidní leukémie pomocí systematické analýzy interaktomu proteinu BCR-ABL
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