Sequence and structural duality: designing peptides to adopt two stable conformations.

Maya J Pandya; Eleonora Cerasoli; Abbey Joseph; Rhys G Stoneman; Eleanor Waite; Derek N Woolfson

doi:10.1021/ja045568c

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Sequence and structural duality: designing peptides to adopt two stable conformations.

Maya J Pandya·Eleonora Cerasoli·Abbey Joseph·Rhys G Stoneman·Eleanor Waite·Derek N Woolfson

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Abstract

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.

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Amino Acid Sequence Circular Dichroism Cysteine Hydrophobic and Hydrophilic Interactions Leucine Zippers Lysine Models, Molecular Molecular Sequence Data Molecular Weight Oligopeptides Peptides Protein Conformation Protein Engineering Journal Article Research Support, Non-U.S. Gov't

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Maya J Pandya, Eleonora Cerasoli, Abbey Joseph, Rhys G Stoneman, Eleanor Waite, Derek N Woolfson. 2004-12-29. Sequence and structural duality: designing peptides to adopt two stable conformations.. https://doi.org/10.1021/ja045568c

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