%0 Journal Article
%A Leitz, Anna
%A Kav, Batuhan
%A Liu, Xiyang
%A Fatafta, Hebah
%A Jankowski, Vera
%A Aggeler, Bastian
%A Gao, Yingying
%A Martin, Ina Verena
%A Vogt, Kristian
%A Kramann, Rafael
%A Ostendorf, Tammo
%A Rauen, Thomas
%A Strodel, Birgit
%A Raffetseder, Ute
%T Guanidinylation of the cold shock protein YB ‐1: Molecular basis, structural changes and Notch‐3 receptor binding
%J Protein science
%V 34
%N 7
%@ 0961-8368
%C Hoboken, NJ
%I Wiley
%M FZJ-2025-03008
%P e70188
%D 2025
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ 40563206
%U <Go to ISI:>//WOS:001516471300001
%R 10.1002/pro.70188
%U https://juser.fz-juelich.de/record/1043722