Title :

A Central Cysteine Residue Is Essential for the Thermal Stability and Function of SUMO-1 Protein and SUMO-1 Peptide-Protein Conjugates

Author(s) :

Drobecq, Hervé [Auteur]
Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 [M3T]
Boll, Emmanuelle [Auteur]
Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 [M3T]
Sénéchal, Magalie [Auteur]
Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 [M3T]
Desmet, Rémi [Auteur]
Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 [M3T]
Saliou, Jean-Michel [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Lacapère, Jean-Jacques [Auteur]
Laboratoire des biomolécules [LBM UMR 7203]
Mougel, Alexandra [Auteur]
Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 [M3T]
Vicogne, Jérôme [Auteur]
Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 [M3T]
Melnyk, Oleg [Auteur]
Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 [M3T]

Journal title :

Bioconjugate Chemistry

Pages :

1540-1546

Publisher :

American Chemical Society

Publication date :

2016-06

ISSN :

1043-1802

HAL domain(s) :

Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire

English abstract : [en]

SUMOylation constitutes a major post-translational modification (PTM) used by the eukaryote cellular machinery to modulate protein interactions of the targeted proteins. The small ubiquitin-like modifier-1 (SUMO-1) features ...
Show more >SUMOylation constitutes a major post-translational modification (PTM) used by the eukaryote cellular machinery to modulate protein interactions of the targeted proteins. The small ubiquitin-like modifier-1 (SUMO-1) features a central and conserved cysteine residue (Cys52) that is located in the hydrophobic core of the protein and in tight contact with Phe65, suggesting the occurrence of an S/pi interaction. To investigate the importance of Cys52 on SUMO-1 thermal stability and biochemical properties, we produced by total chemical synthesis SUMO-1 or SUMO-1 Cys52Ala peptide protein conjugates featuring a native isopeptidic bond between SUMO-1 and a peptide derived from p53 tumor suppressor protein. The Cys52Ala modification perturbed SUMO-1 secondary structure and resulted in a dramatic loss of protein thermal stability. Moreover, the cleavage of the isopeptidic bond by the deconjugating enzyme Upl1 was significantly less efficient than for the wild-type conjugate. Similarly, the in vitro SUMOylation of RanGap1 by E1/E2 conjugating enzymes was significantly less efficient with the SUMO-1 C52A analog compared to wild-type SUMO-1. These data demonstrate the critical role of Cys52 in maintaining SUMO-1 conformation and function and the importance of keeping this cysteine intact for the study of SUMO-1 protein conjugates.Show less >

Language :

Anglais

Popular science :

Non

ANR Project :

Alliance française contre les maladies parasitaires

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL