Cysteine oxidation and disulfide formation in the ribosomal exit tunnel.


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Authors
Schulte, Linda 
Mao, Jiafei 
Sreeramulu, Sridhar 
Kudlinzki, Denis 
Abstract

Understanding the conformational sampling of translation-arrested ribosome nascent chain complexes is key to understand co-translational folding. Up to now, coupling of cysteine oxidation, disulfide bond formation and structure formation in nascent chains has remained elusive. Here, we investigate the eye-lens protein γB-crystallin in the ribosomal exit tunnel. Using mass spectrometry, theoretical simulations, dynamic nuclear polarization-enhanced solid-state nuclear magnetic resonance and cryo-electron microscopy, we show that thiol groups of cysteine residues undergo S-glutathionylation and S-nitrosylation and form non-native disulfide bonds. Thus, covalent modification chemistry occurs already prior to nascent chain release as the ribosome exit tunnel provides sufficient space even for disulfide bond formation which can guide protein folding.

Description

Funder: DFG graduate college: CLiC State of Hesse HMWK: BMRZ

Keywords
Cryoelectron Microscopy, Cysteine, Disulfides, Glutathione, Magnetic Resonance Spectroscopy, Mass Spectrometry, Models, Molecular, Mutation, Oxidation-Reduction, Protein Biosynthesis, Protein Conformation, Protein Folding, Ribosomes, S-Nitrosothiols, gamma-Crystallins
Journal Title
Nat Commun
Conference Name
Journal ISSN
2041-1723
2041-1723
Volume Title
11
Publisher
Springer Science and Business Media LLC