TY  - JOUR
AU  - Leitz, Anna
AU  - Kav, Batuhan
AU  - Liu, Xiyang
AU  - Fatafta, Hebah
AU  - Jankowski, Vera
AU  - Aggeler, Bastian
AU  - Gao, Yingying
AU  - Martin, Ina Verena
AU  - Vogt, Kristian
AU  - Kramann, Rafael
AU  - Ostendorf, Tammo
AU  - Rauen, Thomas
AU  - Strodel, Birgit
AU  - Raffetseder, Ute
TI  - Guanidinylation of the cold shock protein YB ‐1: Molecular basis, structural changes and Notch‐3 receptor binding
JO  - Protein science
VL  - 34
IS  - 7
SN  - 0961-8368
CY  - Hoboken, NJ
PB  - Wiley
M1  - FZJ-2025-03008
SP  - e70188
PY  - 2025
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 40563206
UR  - <Go to ISI:>//WOS:001516471300001
DO  - DOI:10.1002/pro.70188
UR  - https://juser.fz-juelich.de/record/1043722
ER  -