Journal Article

FZJ-2025-03008

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Guanidinylation of the cold shock protein YB ‐1: Molecular basis, structural changes and Notch‐3 receptor binding

Leitz, A. ; Kav, B. ; Liu, X. ; Fatafta, H. ; Jankowski, V. ; Aggeler, B. ; Gao, Y. ; Martin, I. V. ; Vogt, K. ; Kramann, R. ; Ostendorf, T. ; Rauen, T. ; Strodel, B. (Corresponding author)FZJ* ; Raffetseder, U. (Corresponding author)

2025
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/pro.70188  doi:10.34734/FZJ-2025-03008

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.

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Contributing Institute(s):

1. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)

Appears in the scientific report 2025

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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