Analysis of binding interfaces of the human scaffold protein AXIN1 by peptide microarrays

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F18%3A00101698" target="_blank" >RIV/00216224:14310/18:00101698 - isvavai.cz</a>

Alternative codes found

RIV/68081707:_____/18:00501855

Result on the web

<a href="http://www.jbc.org/content/293/42/16337" target="_blank" >http://www.jbc.org/content/293/42/16337</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1074/jbc.RA118.005127" target="_blank" >10.1074/jbc.RA118.005127</a>

Result language

angličtina

Original language name

Analysis of binding interfaces of the human scaffold protein AXIN1 by peptide microarrays

Original language description

Intrinsically disordered regions (IDRs) are protein regions that lack persistent secondary or tertiary structure under native conditions. IDRs represent &gt;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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

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Volume of the periodical

293

Issue of the periodical within the volume

42

Country of publishing house

US - UNITED STATES

Number of pages

11

Pages from-to

16337-16347

UT code for WoS article

000447833600018

EID of the result in the Scopus database

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