Protein folding guides disulfide bond formation #MMPMID26297249
Qin M; Wang W; Thirumalai D
Proc Natl Acad Sci U S A 2015[Sep]; 112 (36): 11241-6 PMID26297249show ga
Anfinsen inferred the principles of protein folding by studying a protein containing four disulfide bonds in the native state. However, how protein folding drives disulfide bond formation is poorly understood despite the role such proteins play in variety of extracellular and intracellular functions. We developed a method to mimic the complex chemistry of disulfide bond formation in molecular simulations, which is used to decipher the mechanism of folding of bovine pancreatic trypsin inhibitor. The flux to the native state is through a complex network of native-like states. Crucially, we establish that it is the conformational folding of the protein that directs disulfide bond formation. Testable predictions and implications for enzyme-catalyzed folding of disulfide proteins in vivo are outlined.
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Proc+Natl+Acad+Sci+U+S+A 2015 ; 112 (36): 11241-6
