| HARNOŠ, Jakub, Jan RYNEŠ, Pavlína VÍŠKOVÁ, Silvie TRANTÍRKOVÁ, Lola Murielle BAJARD ÉP.ESNER, Lukáš TRANTÍREK a 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, roč. 293, č. 42, s. 16337-16347. ISSN 0021-9258. Dostupné z: https://dx.doi.org/10.1074/jbc.RA118.005127. |
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@article{1495637,
author = {Harnoš, Jakub and Ryneš, Jan and Víšková, Pavlína and Trantírková, Silvie and Bajard ép.Esner, Lola Murielle and Trantírek, Lukáš and Bryja, Vítězslav},
article_location = {Bethesda, USA},
article_number = {42},
doi = {http://dx.doi.org/10.1074/jbc.RA118.005127},
keywords = {peptide array; scaffold protein; axin; serine; threonine protein kinase; p53; Myc (c-Myc); casein kinase 1E; dishevelled; intrinsically disordered region; Wnt pathway},
language = {eng},
issn = {0021-9258},
journal = {Journal of Biological Chemistry},
title = {Analysis of binding interfaces of the human scaffold protein AXIN1 by peptide microarrays},
url = {http://www.jbc.org/content/293/42/16337},
volume = {293},
year = {2018}
}
TY - JOUR
ID - 1495637
AU - Harnoš, Jakub - Ryneš, Jan - Víšková, Pavlína - Trantírková, Silvie - Bajard ép.Esner, Lola Murielle - Trantírek, Lukáš - Bryja, Vítězslav
PY - 2018
TI - Analysis of binding interfaces of the human scaffold protein AXIN1 by peptide microarrays
JF - Journal of Biological Chemistry
VL - 293
IS - 42
SP - 16337-16347
EP - 16337-16347
PB - Amer. Soc. Biochem. Mol. Biol.
SN - 00219258
KW - peptide array
KW - scaffold protein
KW - axin
KW - serine
KW - threonine protein kinase
KW - p53
KW - Myc (c-Myc)
KW - casein kinase 1E
KW - dishevelled
KW - intrinsically disordered region
KW - Wnt pathway
UR - http://www.jbc.org/content/293/42/16337
L2 - http://www.jbc.org/content/293/42/16337
N2 - 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.
ER -
HARNOŠ, Jakub, Jan RYNEŠ, Pavlína VÍŠKOVÁ, Silvie TRANTÍRKOVÁ, Lola Murielle BAJARD ÉP.ESNER, Lukáš TRANTÍREK a Vítězslav BRYJA. Analysis of binding interfaces of the human scaffold protein AXIN1 by peptide microarrays. \textit{Journal of Biological Chemistry}. Bethesda, USA: Amer. Soc. Biochem. Mol. Biol., 2018, roč.~293, č.~42, s.~16337-16347. ISSN~0021-9258. Dostupné z: https://dx.doi.org/10.1074/jbc.RA118.005127.
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