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.
Chemistry Department, Princeton University, New Jersey 80544.
L C
LC
Wu
P B
PB
Laub
G A
GA
Elöve
J
J
Carey
H
H
Roder
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