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.
Krishna
Mallela M G
MM
Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6059, USA. kmallela@mail.med.upenn.edu
Maity
Haripada
H
Rumbley
Jon N
JN
Englander
S Walter
SW
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