A noncovalent peptide complex as a model for an early folding intermediate of cytochrome c.
Horse heart cytochrome c is one of a small number of proteins for which the folding pathway has been elucidated in structural detail by pulsed hydrogen exchange and NMR. Those studies indicated that a partially folded intermediate with interacting N- and C-terminal helices is formed at an early stage of folding when most of the chain is still disordered. This report describes a peptide model for this early intermediate, consisting of a noncovalent complex between a heme-containing N-terminal fragment (residues 1-38) and a synthetic peptide corresponding to the C-terminal helix (residues 87-104). Far-UV circular dichroism and proton NMR indicate that the isolated peptides are largely disordered, but when combined, they form a flexible, yet tightly bound complex with enhanced helical structure. These results emphasize the importance of interactions between marginally stable elements of secondary structure in forming tertiary subdomains in protein folding.
Wu
L C
LC
Chemistry Department, Princeton University, New Jersey 80544.
Laub
P B
PB
Elöve
G A
GA
Carey
J
J
Roder
H
H
D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D003574:Cytochrome c Group / Q000737:chemistry / Q000378:metabolism*; D006418:Heme / Q000032:analysis; D006736:Horses; D009682:Magnetic Resonance Spectroscopy; D008961:Models, Structural; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary
D003574:Cytochrome c Group; D010455:Peptides; D006418:Heme