Sequence and structural duality: designing peptides to adopt two stable conformations.
To improve our understanding of conformational transitions in proteins, we are attempting the de novo design of peptides that switch structural state. Here, we describe coiled-coil peptides with sequence and structural duality; that is, features compatible with two different coiled-coil motifs superimposed within the same sequence. Specifically, we promoted a parallel leucine-zipper dimer under reducing conditions, and a monomeric helical hairpin in an intramolecularly disulfide bridged state. Using an iterative process, we engineered peptides that formed stable structures consistent with both targets under the different conditions. Finally, for one of the designs, we demonstrated a one-way switch from the helical hairpin to the coiled-coil dimer upon addition of disulfide-reducing agents.
Pandya
Maya J
MJ
Department of Biochemistry, John Maynard-Smith Building, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, United Kingdom.
Cerasoli
Eleonora
E
Joseph
Abbey
A
Stoneman
Rhys G
RG
Waite
Eleanor
E
Woolfson
Derek N
DN
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D003545:Cysteine / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D016350:Leucine Zippers; D008239:Lysine / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D015202:Protein Engineering
D009842:Oligopeptides; D010455:Peptides; C044514:glycyl-glycyl-cysteine; D008239:Lysine; D003545:Cysteine