Cysteines as Redox Molecular Switches and Targets of Disease

Frontiers in Molecular Neuroscience

卷:10

Annamaria Fra¹  Edgar D. Yoboue²  Roberto Sitia² 

[1] Department of Molecular and Translational Medicine, University of BresciaBrescia, Italy;

[2] Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific InstituteMilan, Italy;

[3] Division of Genetics and Cell Biology, Vita-Salute San Raffaele UniversityMilan, Italy;

关键词: cellular redoxstasis;    cysteine mutation;    signaling pathways;    disulfide bonding;    protein misfolding;   

DOI  :  10.3389/fnmol.2017.00167

来源: DOAJ

【 摘 要 】

Thiol groups can undergo numerous modifications, making cysteine a unique molecular switch. Cysteine plays structural and regulatory roles as part of proteins or glutathione, contributing to maintain redox homeostasis and regulate signaling within and amongst cells. Not surprisingly therefore, cysteines are associated with many hereditary and acquired diseases. Mutations in the primary protein sequence (gain or loss of a cysteine) are most frequent in membrane and secretory proteins, correlating with the key roles of disulfide bonds. On the contrary, in the cytosol and nucleus, aberrant post-translational oxidative modifications of thiol groups, reflecting redox changes in the surrounding environment, are a more frequent cause of dysregulation of protein function. This essay highlights the regulatory functions performed by protein cysteine residues and provides a framework for understanding how mutation and/or (in)activation of this key amino acid can cause disease.

【 授权许可】

Unknown