Branching in the sequential folding pathway of cytochrome c.
Previous results indicate that the folding pathways of cytochrome c and other proteins progressively build the target native protein in a predetermined stepwise manner by the sequential formation and association of native-like foldon units. The present work used native state hydrogen exchange methods to investigate a structural anomaly in cytochrome c results that suggested the concerted folding of two segments that have little structural relationship in the native protein. The results show that the two segments, an 18-residue omega loop and a 10-residue helix, are able to unfold and refold independently, which allows a branch point in the folding pathway. The pathway that emerges assembles native-like foldon units in a linear sequential manner when prior native-like structure can template a single subsequent foldon, and optional pathway branching is seen when prior structure is able to support the folding of two different foldons.
Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6059, USA. kmallela@mail.med.upenn.edu
Mallela M G
MM
Krishna
Haripada
H
Maity
Jon N
JN
Rumbley
S Walter
SW
Englander
D000577:Amides / Q000737:chemistry; D000818:Animals; D045304:Cytochromes c / Q000737:chemistry* / Q000378:metabolism*; D041961:Deuterium Exchange Measurement; D004795:Enzyme Stability; D006736:Horses; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary
D000577:Amides; D045304:Cytochromes c