The roles of side chain and backbone in protein structure probed with glycine- and sarcosine-rich synthetic leucine zipper peptides.
The protein folding problem has long been a formidable challenge. Here we present a synthetic natural motif approach that exploits small preexisting structural models for the dissection of forces important in protein folding. An example for this approach is shown in the modification of a 31-residue leucine zipper peptide with the helix-breaking amino acid glycine and the hydrogen bond-breaking imino acid sarcosine. Circular dichroism and NMR experiments have shown that the glycine-modified leucine zipper peptide adopts a stable helical conformation similar to the native conformation while the sarcosine-modified leucine zipper peptide adopts a random coil conformation. These results provide valuable insight into the current controversy over the relative importance of long-range side chain-side chain interactions versus local backbone interactions in protein structure and suggest that the natural motif strategy may represent a useful model to study protein folding.
Butcher
D J
DJ
Kimmel Cancer Institute, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, 19107, USA.
Luo
Z
Z
Huang
Z
Z
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D005998:Glycine / Q000737:chemistry; D016350:Leucine Zippers; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D012521:Sarcosine / Q000737:chemistry
D010455:Peptides; D011506:Proteins; D005998:Glycine; D012521:Sarcosine