Folding of immunogenic peptide fragments of proteins in water solution. II. The nascent helix.
1H nuclear magnetic resonance experiments indicate formation of secondary structures in water solutions of a synthetic immunogenic peptide of sequence EVVPHKKMHKDFLEKIGGL corresponding to the C-helix (residues 69 to 87) of myohemerythrin. The conformational ensemble consists of a set of turn-like structures, distributed over the C-terminal half of the peptide and rapidly interconverting by way of unfolded states. These structures, termed nascent helix, are stabilized into helical structure with long-range order in water/trifluorethanol mixtures. Circular dichroism measurements confirm the presence of 50% helix in water/trifluoroethanol but show no evidence of helicity in water solutions of the peptide. It is apparent that no one member of the transient set of helical conformations which constitutes the nascent helix is sufficiently long to be detectable by circular dichroism experiments. No preferred conformations could be detected by nuclear magnetic resonance in the N-terminal half of the peptide, either in water or water/trifluoroethanol mixtures. This region of the peptide is stabilized in helix by long-range interactions in the folded protein. The possible role of nascent secondary structure in induction of antipeptide antibodies and in initiation of protein folding is discussed.
Department of Molecular Biology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
H J
HJ
Dyson
M
M
Rance
R A
RA
Houghten
P E
PE
Wright
R A
RA
Lerner
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006422:Hemerythrin / Q000031:analogs & derivatives / Q000276:immunology; D009682:Magnetic Resonance Spectroscopy; D008667:Metalloproteins / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011487:Protein Conformation; D012996:Solutions; D014270:Trifluoroethanol; D014867:Water
D006422:Hemerythrin; D008667:Metalloproteins; D010446:Peptide Fragments; D012996:Solutions; C008571:myohemerythrin; D014867:Water; D014270:Trifluoroethanol