title: Synthetic peptides probe folding initiation sites in platelet factor-4: stable chain reversal found within the hydrophobic sequence LIATLKNGRKISL.
abstract: Platelet factor-4 (PF4) is a 70-residue protein which contains a 3-stranded antiparallel beta-sheet domain on to which is folded a C-terminal alpha-helix and an aperiodic N-terminal region. In this study, three peptides derived from the beta-sheet (residues 24-46 and 38-57) and helix (residues 57-70) domains have been synthesized and studied in aqueous solution by CD and NMR. While peptides 24-46 and 56-70 demonstrate some weak conformational preferences, peptide 38-57 maintains a relatively well-defined, NOE-rich chain reversal sequence, L45-K46-N47-G48-R49-K50, which apparently is stabilized by hydrophobic side-chain interactions from the flanking sequences L41-L45 and I51-L53. Some helix-like conformational populations are noted in the native PF4 I42-A43-T44-L45 beta-strand segment. NOE-based distance geometry calculations yield native-like conformations within the L45-K50 sequence. Among 40 structures, backbone RMS deviations range from 0.5 to 1.2 A, and compared to the same sequence in native PF4, the average RMS deviation is 1.1 A. These results suggest that beta-sheet/turn residues L41-L53 present a folding initiation site on the PF4 folding pathway.
authors.affiliation: Department of Biochemistry, University of Minnesota, Minneapolis 55455.
authors.forename: E
authors.initials: E
authors.lastname: Ilyina
authors.forename: R
authors.initials: R
authors.lastname: Milius
authors.forename: K H
authors.initials: KH
authors.lastname: Mayo
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D015335:Molecular Probes / Q000138:chemical synthesis; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis*; D010978:Platelet Factor 4 / Q000737:chemistry*; D017510:Protein Folding; D016415:Sequence Alignment
chemical_list: D015335:Molecular Probes; D010455:Peptides; D010978:Platelet Factor 4