The partially folded conformation of the Cys-30 Cys-51 intermediate in the disulfide folding pathway of bovine pancreatic trypsin inhibitor.
The best-characterized protein folding pathway is that of bovine pancreatic trypsin inhibitor, which folds from the reduced form through a series of disulfide bond intermediates. The crucial one-disulfide intermediate of bovine pancreatic trypsin inhibitor with the disulfide bond between Cys-30 and Cys-51 is shown here to have a partially folded conformation in which the major elements of secondary structure interact via a core of apolar side chains, which resembles part of the native conformation. The stability of this structure can account for the predominance of this one-disulfide intermediate during folding. Much of the remaining one-third of the polypeptide chain, in particular the N-terminal 14 residues, is largely disordered; this accounts for the ability of this intermediate to form readily any of the three possible second disulfide bonds involving Cys-5, -14, and -38. The partially folded conformation of this intermediate provides direct evidence for the importance of native-like interactions between elements of secondary structure in directing protein folding, which is assumed in many studies.
van Mierlo
C P
CP
Medical Research Council Laboratory of Molecular Biology, Cambridge, England.
Darby
N J
NJ
Creighton
T E
TE
D000595:Amino Acid Sequence; D000818:Animals; D007611:Aprotinin / Q000737:chemistry*; D002417:Cattle; D003545:Cysteine; D004220:Disulfides / Q000737:chemistry*; D006859:Hydrogen; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D011487:Protein Conformation
D004220:Disulfides; D006859:Hydrogen; D007611:Aprotinin; D003545:Cysteine