A Set of de Novo Designed Parallel Heterodimeric Coiled Coils with Quantified Dissociation Constants in the Micromolar to Sub-nanomolar Regime

Franziska Thomas, Aimee L. Boyle, Antony J. Burton, Derek N. Woolfson*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

100 Citations (Scopus)

Abstract

The availability of peptide and protein components that fold to defined structures with tailored stabilities would facilitate rational protein engineering and synthetic biology. We have begun to generate a toolkit of such components based on de novo designed coiled-coil peptides that mediate protein-protein interactions. Here, we present a set of coiled-coil heterodimers to add to the toolkit. The lengths of the coiled-coil regions are 21, 24, or 28 residues, which deliver dissociation constants in the micromolar to sub-nanomolar range. In addition, comparison of two related series of peptides highlights the need for including polar residues within the hydrophobic interfaces, both to specify the dimer state over alternatives and to fine-tune the dissociation constants.

Original languageEnglish
Pages (from-to)5161-5166
Number of pages6
JournalJournal of the American Chemical Society
Volume135
Issue number13
DOIs
Publication statusPublished - 2 Apr 2013

Structured keywords

  • Bristol BioDesign Institute
  • BCS and TECS CDTs

Keywords

  • DIMERIZATION
  • PEPTIDE
  • PROTEIN-DESIGN
  • STABILITY
  • MEMBRANE-FUSION
  • GCN4 LEUCINE-ZIPPER
  • DOMAINS
  • THERMODYNAMIC SCALE
  • SPECIFICITY
  • SYNTHETIC BIOLOGY

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