Specifying conformational heterogeneity of multi-domain proteins at atomic resolution.

Protein Conformation Ubiquitin / metabolism Polyubiquitin / chemistry Magnetic Resonance Spectroscopy
MD simulations NMR spectroscopy click chemistry conformational ensembles conformational heterogeneity multi-domain proteins paramagnetic relaxation enhancement protein dynamics spin relaxation ubiquitin chains

Journal

Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697

Informations de publication

Date de publication:
05 10 2023
Historique:
received: 03 03 2023
revised: 02 06 2023
accepted: 14 07 2023
medline: 9 10 2023
pubmed: 10 8 2023
entrez: 9 8 2023
Statut: ppublish

Résumé

The conformational landscape of multi-domain proteins is inherently linked to their specific functions. This also holds for polyubiquitin chains that are assembled by two or more ubiquitin domains connected by a flexible linker thus showing a large interdomain mobility. However, molecular recognition and signal transduction are associated with particular conformational substates that are populated in solution. Here, we apply high-resolution NMR spectroscopy in combination with dual-scale MD simulations to explore the conformational space of K6-, K29-, and K33-linked diubiquitin molecules. The conformational ensembles are evaluated utilizing a paramagnetic cosolute reporting on solvent exposure plus a set of complementary NMR parameters. This approach unravels a conformational heterogeneity of diubiquitins and explains the diversity of structural models that have been determined for K6-, K29-, and K33-linked diubiquitins in free and ligand-bound states so far. We propose a general application of the approach developed here to demystify multi-domain proteins occurring in nature.

Identifiants

DOI: 10.1016/j.str.2023.07.008 PMID: 37557171
pubmed: 37557171
pii: S0969-2126(23)00250-2
doi: 10.1016/j.str.2023.07.008
pii:
doi:

Substances chimiques

Ubiquitin 0
Polyubiquitin 120904-94-1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1259-1274.e10

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Tobias Schneider (T)

Department of Chemistry, University of Konstanz, 78457 Konstanz, Germany; Konstanz Research School Chemical Biology, University of Konstanz, 78457 Konstanz, Germany.

Kevin Sawade (K)

Department of Chemistry, University of Konstanz, 78457 Konstanz, Germany; Graduate School Chemistry, University of Konstanz, 78457 Konstanz, Germany.

Frederic Berner (F)

Department of Chemistry, University of Konstanz, 78457 Konstanz, Germany; Konstanz Research School Chemical Biology, University of Konstanz, 78457 Konstanz, Germany.

Christine Peter (C)

Department of Chemistry, University of Konstanz, 78457 Konstanz, Germany; Konstanz Research School Chemical Biology, University of Konstanz, 78457 Konstanz, Germany.

Michael Kovermann (M)

Department of Chemistry, University of Konstanz, 78457 Konstanz, Germany; Konstanz Research School Chemical Biology, University of Konstanz, 78457 Konstanz, Germany. Electronic address: michael.kovermann@uni-konstanz.de.

Articles similaires

Drug repurposing against fucosyltransferase-2 via docking, STD-NMR, and molecular dynamic simulation studies.

Muhammad Atif, Humaira Zafar, Atia-Tul- Wahab et al.
1.00
Fucosyltransferases Drug Repositioning Molecular Docking Simulation Molecular Dynamics Simulation Humans

Nitrile glove composition and performance-Substandard properties and inaccurate packaging information.

Ashley Herkins, Sriloy Dey, Dan Conroy et al.
1.00
Nitriles Tensile Strength Materials Testing Gloves, Protective Product Packaging

Structural basis for molecular assembly of fucoxanthin chlorophyll

Koji Kato, Yoshiki Nakajima, Jian Xing et al.
1.00
Diatoms Photosystem I Protein Complex Chlorophyll Binding Proteins Cryoelectron Microscopy Light-Harvesting Protein Complexes

Ubiquitination regulates autophagy in cancer: simple modifications, promising targets.

Yihui Wu, Yifei Chen, Xianyan Tian et al.
1.00
Autophagy Humans Neoplasms Ubiquitination Animals

Classifications MeSH

questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Specifying conformational heterogeneity of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Ubiquitines › Ubiquitine › Specifying conformational heterogeneity of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Ubiquitines › Ubiquitine › Polyubiquitine › Specifying conformational heterogeneity of...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Analyse spectrale › Spectroscopie par résonance magnétique › Specifying conformational heterogeneity of...