Dataset Information

S-nitrosation of proteins relevant to Alzheimer’s disease during early stages of neurodegeneration

ABSTRACT: Protein S-nitrosation (SNO-protein) is a post-translational modification in which a cysteine (Cys) residue is modified by nitric oxide (SNO-Cys). SNO-proteins impact many biological systems, but their identification has been technically challenging. We developed a chemical proteomic strategy - SNOTRAP (SNO trapping by triaryl phosphine) -that allows improved identification of SNO-proteins by mass spectrometry. We found that S-nitrosation is elevated during early stages of neurodegeneration, preceding cognitive decline. We identified changes in the SNOproteome during early neurodegeneration that are potentially relevant for synapse function, metabolism, and Alzheimer’s disease pathology. SNO-proteome analysis further reveals a potential linear motif for SNO-Cys sites that are altered during neurodegeneration. Our strategy can be applied to multiple cellular and disease contexts and can reveal signaling networks that aid drug development.

INSTRUMENT(S): 6520A Quadrupole Time-of-Flight LC/MS

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Alzheimer's Disease

SUBMITTER: John Wishnok

LAB HEAD: Steven R. Tannenbaum

PROVIDER: PXD003802 | Pride | 2016-03-31

REPOSITORIES: Pride

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S-nitrosation of proteins relevant to Alzheimer's disease during early stages of neurodegeneration.

Seneviratne Uthpala U Nott Alexi A Bhat Vadiraja B VB Ravindra Kodihalli C KC Wishnok John S JS Tsai Li-Huei LH Tannenbaum Steven R SR

Proceedings of the National Academy of Sciences of the United States of America 20160324 15

Protein S-nitrosation (SNO-protein), the nitric oxide-mediated posttranslational modification of cysteine thiols, is an important regulatory mechanism of protein function in both physiological and pathological pathways. A key first step toward elucidating the mechanism by which S-nitrosation modulates a protein's function is identification of the targeted cysteine residues. Here, we present a strategy for the simultaneous identification of SNO-cysteine sites and their cognate proteins to profile ...[more]

PMID: 27035958

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