title: A natural motif approach to protein design: a synthetic leucine zipper peptide mimics the biological function of the platelet factor 4 protein.
abstract: The design of smaller functional mimics of large proteins has long been an important challenge. In this study we use the natural leucine zipper as a structural template to design a 31-residue peptide analog that mimics the function of the larger platelet factor 4 (PF4) protein. The heparin binding activity of PF4 has been introduced into an unrelated leucine zipper sequence only by virtue of incorporating four lysines of PF4. Circular dichroism and binding experiments have shown that the designed leucine zipper peptide adopts a stable helical conformation and shows significant PF4-like heparin binding activity. These results strongly suggest that the lysine residues play an important role in the binding of PF4 to heparin. The de novo generation of the PF4 function in a designed leucine zipper peptide demonstrates that the leucine zipper motif is a useful scaffold for the design of functional peptides and proteins.
authors.affiliation: Kimmel Cancer Institute, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Butcher
authors.forename: M A
authors.initials: MA
authors.lastname: Kowalska
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: Z
authors.initials: Z
authors.lastname: Luo
authors.forename: S
authors.initials: S
authors.lastname: Shan
authors.forename: Z
authors.initials: Z
authors.lastname: Lu
authors.forename: S
authors.initials: S
authors.lastname: Niewiarowski
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000502:physiology; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000138:chemical synthesis / Q000502:physiology*; D006493:Heparin / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D018375:Neutrophil Activation / Q000187:drug effects; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology / Q000502:physiology*; D010978:Platelet Factor 4 / Q000737:chemistry* / Q000502:physiology*; D015202:Protein Engineering; D011494:Protein Kinases / Q000138:chemical synthesis / Q000502:physiology*; D018123:Receptors, Interleukin / Q000502:physiology; D023062:Receptors, Interleukin-8A; D029701:Saccharomyces cerevisiae Proteins; D013329:Structure-Activity Relationship
chemical_list: D015703:Antigens, CD; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D016209:Interleukin-8; D010455:Peptides; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D029701:Saccharomyces cerevisiae Proteins; D010978:Platelet Factor 4; D006493:Heparin; D011494:Protein Kinases