期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 39, 页码 16958-16963出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1008036107
关键词
cysteine modification; nitric oxide; S-nitrosation; posttranslational modification; proteomics
资金
- National Institutes of Health [AG13966, HL054926]
- National Institute of Environmental Health Sciences Center of Excellence in Environmental Toxicology [ES013508]
- National Institute of General Medical Sciences [F31GM085903]
S-nitrosylation, the selective posttranslational modification of protein cysteine residues to form S-nitrosocysteine, is one of the molecular mechanisms by which nitric oxide influences diverse biological functions. In this study, unique MS-based proteomic approaches precisely pinpointed the site of S-nitrosylation in 328 peptides in 192 proteins endogenously modified in WT mouse liver. Structural analyses revealed that S-nitrosylated cysteine residues were equally distributed in hydrophobic and hydrophilic areas of proteins with an average predicted pK(a) of 10.01 +/- 2.1. S-nitrosylation sites were over-represented in a-helices and under-represented in coils as compared with unmodified cysteine residues in the same proteins (chi(2) test, P < 0.02). A quantile-quantile probability plot indicated that the distribution of S-nitrosocysteine residues was skewed toward larger surface accessible areas compared with the unmodified cysteine residues in the same proteins. Seventy percent of the S-nitrosylated cysteine residues were surrounded by negatively or positively charged amino acids within a 6-angstrom distance. The location of cysteine residues in a-helices and coils in highly accessible surfaces bordered by charged amino acids implies site directed S-nitrosylation mediated by protein-protein or small molecule interactions. Moreover, 13 modified cysteine residues were coordinated with metals and 15 metalloproteins were endogenously modified supporting metal-catalyzed S-nitrosylation mechanisms. Collectively, the endogenous S-nitrosoproteome in the liver has structural features that accommodate multiple mechanisms for selective site-directed S-nitrosylation.
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