SUMO's intrinsically disordered N-terminus is an intramolecular inhibitor of SUMO - SIM interactions

Abstract:

Small Ubiquitin-related modifiers of the SUMO family regulate thousands of proteins in eukaryotic cells. Many SUMO substrates, effectors and enzymes carry short motifs (SIMs) that mediate low affinity interactions with SUMO proteins. This raises the question how specificity is achieved in target selection, SUMO paralogue choice and SUMO-dependent interactions. A unique but poorly understood feature of SUMO proteins is their intrinsically disordered N-terminus. We reveal a function for N-termini of human, C. elegans, and yeast SUMO proteins as intramolecular inhibitors of SUMO-SIM interactions. Mutational analyses, NMR spectroscopy, and Molecular Dynamics simulations indicate that SUMO's N-terminus can inhibit SIM binding by fast and fuzzy interactions with SUMO‘s core. Deletion of the C. elegans SUMO1 N-terminus leads to p53-dependent apoptosis during germline development, indicating an important role of SUMO's N-termini in DNA damage repair. Our findings reveal a mechanism of disorder-based autoinhibition that contributes to the specificity of SUMOylation and SUMO-dependent interactions.

SEEK ID: https://publications.h-its.org/publications/1763

DOI: 10.1101/2024.01.04.574143

Research Groups: Molecular Biomechanics

Publication type: Journal

Journal: bioRxiv

Publisher: Cold Spring Harbor Laboratory

Citation: bioRxiv

Date Published: 5th Jan 2024

URL:

Registered Mode: manually

Authors: Stefan Richter, Fan Jin, Tobias Ritterhoff, Aleksandra Fergin, Eric Maurer, Andrea Frank, Alex Hajnal, Rachel Klevit, Frauke Gräter, Annette Flotho, Frauke Melchior

help Submitter
Citation
Richter, S. M., Jin, F., Ritterhoff, T., Fergin, A., Maurer, E., Frank, A., Daube, M., Hajnal, A., Klevit, R., Gräter, F., Flotho, A., & Melchior, F. (2024). The intrinsically disordered N-terminus of SUMO1 is an intramolecular inhibitor of SUMO1 interactions. In []. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2024.01.04.574143
Activity

Views: 1773

Created: 8th Jan 2024 at 09:21

Last updated: 5th Mar 2024 at 21:25

help Tags

This item has not yet been tagged.

help Attributions

None

Powered by
(v.1.15.2)
Copyright © 2008 - 2024 The University of Manchester and HITS gGmbH