Disulfide-linked protein folding pathways.
Determining the mechanism by which proteins attain their native structure is an important but difficult problem in basic biology. The study of protein folding is difficult because it involves the identification and characterization of folding intermediates that are only very transiently present. Disulfide bond formation is thermodynamically linked to protein folding. The availability of thiol trapping reagents and the relatively slow kinetics of disulfide bond formation have facilitated the isolation, purification, and characterization of disulfide-linked folding intermediates. As a result, the folding pathways of several disulfide-rich proteins are among the best known of any protein. This review discusses disulfide bond formation and its relationship to protein folding in vitro and in vivo.
Mamathambika
Bharath S
BS
Biophysics Graduate Program, University of Michigan, Ann Arbor, Michigan 48109, USA. bharath@umich.edu
Bardwell
James C
JC
D000818:Animals; D002384:Catalysis; D004220:Disulfides / Q000737:chemistry*; D006629:Hirudins / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D011487:Protein Conformation; D017510:Protein Folding; D012259:Ribonuclease, Pancreatic / Q000737:chemistry / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000737:chemistry / Q000378:metabolism
D004220:Disulfides; D006629:Hirudins; D013438:Sulfhydryl Compounds; D014359:Trypsin Inhibitor, Kazal Pancreatic; D012259:Ribonuclease, Pancreatic