Two new structured intermediates in the oxidative folding of RNase A.
Two new three-disulfide intermediates have been found to be populated in the oxidative folding pathway of bovine pancreatic ribonuclease A at a low temperature (15 degrees C). These intermediates, des-[26-84] and des-[58-110], possess all but one of the four native disulfide bonds and have a stable tertiary structure, similar to the two previously observed intermediates, des-[65-72] and des-[40-95]. While the latter two des species each lack one surface-exposed disulfide bond, the newly discovered intermediates each lack one buried disulfide bond. The possible involvement of these species in the rate-determining steps during the oxidative folding of RNase A is discussed and a specific role for such species during oxidative folding is suggested.
Welker
E
E
Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301, USA.
Narayan
M
M
Volles
M J
MJ
Scheraga
H A
HA
D000818:Animals; D002417:Cattle; D002852:Chromatography, Ion Exchange; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D010449:Peptide Mapping; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D012259:Ribonuclease, Pancreatic / Q000737:chemistry* / Q000378:metabolism*
D004220:Disulfides; D012259:Ribonuclease, Pancreatic