Cysteinylation of Proteins

Proteins that contain cysteine (Cys) residues normally contain either intrachain or interchain or both intrachain and interchain disulfide bonds. Such Cys residues of proteins are commonly called as paired Cys residues. Some proteins contain free Cys residues that may be due to structural constraints of disulfide bond formation. The free Cys residues of proteins are often referred as unpaired Cys residues. The unpaired Cys residues often form disulfide bonds with free Cys molecules, and such a process is called cysteinylation. In some proteins, trisulfide bond formation between two internal Cys residues of proteins with one free Cys molecule is observed. Trisulfides have been recently observed in some monoclonal antibodies (mAbs). Some organisms use cysteinylation to protect free thiols during oxidative stress. This chapter provides an overview of cysteinylation of proteins with disulfide and trisulfide bonds along with the biological significance of cysteinylation.