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@ARTICLE{Leitz:1043722,
author = {Leitz, Anna and Kav, Batuhan and Liu, Xiyang and Fatafta,
Hebah and Jankowski, Vera and Aggeler, Bastian and Gao,
Yingying and Martin, Ina Verena and Vogt, Kristian and
Kramann, Rafael and Ostendorf, Tammo and Rauen, Thomas and
Strodel, Birgit and Raffetseder, Ute},
title = {{G}uanidinylation of the cold shock protein {YB} ‐1:
{M}olecular basis, structural changes and {N}otch‐3
receptor binding},
journal = {Protein science},
volume = {34},
number = {7},
issn = {0961-8368},
address = {Hoboken, NJ},
publisher = {Wiley},
reportid = {FZJ-2025-03008},
pages = {e70188},
year = {2025},
abstract = {Posttranslational modifications of Y-box binding protein
(YB)-1 are the prerequisite for its very different protein
functions. Here, we investigate the underlying molecular
mechanisms of YB-1 guanidinylation and link increased serum
urea levels as well as the activity of glycine
amidinotransferase (GATM) with guanidinylation. Computer
simulations show changes in stability and conformation of
the YB-1 protein induced by these modifications. In
particular, the secondary structure of the doubly
guanidinylated YB-1 (YB-1-2G) shows a reduced tendency to
form β-sheets, and the modified cold shock domain is more
exposed to the solvent. Protein-protein docking techniques
in conjunction with molecular dynamics simulations confirm
the binding between YB-1 and its receptor Notch-3 at EGF
domains 17-24 but show no significant differences in the
binding behavior of YB-1 and YB-1-2G. This is confirmed in
two different types of receptor-ligand binding assays. In
addition, we demonstrate for the first time a high-affinity
binding of YB-1 to another ligand binding site on the
Notch-3 receptor, thereby achieving effective displacement
of the canonical ligand Jagged. In conclusion, we identified
molecular processes that lead to the guanidinylation of YB-1
and revealed their effects on the structure and binding to
receptor Notch-3.},
cin = {IBI-7},
ddc = {610},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524)},
pid = {G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
pubmed = {40563206},
UT = {WOS:001516471300001},
doi = {10.1002/pro.70188},
url = {https://juser.fz-juelich.de/record/1043722},
}