S-Nitrosylation Induces Structural and Dynamical Changes in a Rhodanese Family Protein.

Cédric Eichmann, Christos Tzitzilonis, Tomohiro Nakamura, Witek Kwiatkowski, Innokentiy Maslennikov, Senyon Choe, Stuart A Lipton, Roland Riek

Journal: Journal of molecular biology 2017;428(19):3737-51

PMID: 27473602

Free Full Text on PubMed Central View on PubMed

Abstract

S-Nitrosylation is well established as an important post-translational regulator in protein function and signaling. However, relatively little is known about its structural and dynamical consequences. We have investigated the effects of S-nitrosylation on the rhodanese domain of the Escherichia coli integral membrane protein YgaP by NMR, X-ray crystallography, and mass spectrometry. The results show that the active cysteine in the rhodanese domain of YgaP is subjected to two competing modifications: S-nitrosylation and S-sulfhydration, which are naturally occurring in vivo. It has been observed that in addition to inhibition of the sulfur transfer activity, S-nitrosylation of the active site residue Cys63 causes an increase in slow motion and a displacement of helix 5 due to a weakening of the interaction between the active site and the helix dipole. These findings provide an example of how nitrosative stress can exert action at the atomic level.

Address: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland.; Structural Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.; Neurodegenerative Disease Center, Scintillon Institute, San Diego, CA 92121, USA.; Neurodegenerative Disease Center, Scintillon Institute, San Diego, CA 92121, USA; Department of Neurosciences, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA; Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.; Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland; Structural Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: [email protected].

DOI: 10.1016/j.jmb.2016.07.010