Design of Protein-Peptide Interaction Modules for Assembling Supramolecular Structures in Vivo and in Vitro

ACS Chem Biol. 2015 Sep 18;10(9):2108-15. doi: 10.1021/acschembio.5b00415. Epub 2015 Jul 17.

Abstract

Synthetic biology and protein origami both require protein building blocks that behave in a reliable, predictable fashion. In particular, we require protein interaction modules with known specificity and affinity. Here, we describe three designed TRAP (Tetratricopeptide Repeat Affinity Protein)-peptide interaction pairs that are functional in vivo. We show that each TRAP binds to its cognate peptide and exhibits low cross-reactivity with the peptides bound by the other TRAPs. In addition, we demonstrate that the TRAP-peptide interactions are functional in many cellular contexts. In extensions of these designs, we show that the binding affinity of a TRAP-peptide pair can be systematically varied. The TRAP-peptide pairs we present thus represent a powerful set of new building blocks that are suitable for a variety of applications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Escherichia coli / chemistry
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / metabolism
  • HEK293 Cells
  • HSP90 Heat-Shock Proteins / chemistry
  • HSP90 Heat-Shock Proteins / metabolism
  • HeLa Cells
  • Homeodomain Proteins / chemistry
  • Homeodomain Proteins / metabolism
  • Humans
  • Models, Molecular
  • Peptides / chemistry
  • Peptides / metabolism*
  • Protein Interaction Domains and Motifs*
  • Protein Interaction Maps*
  • Proteins / chemistry
  • Proteins / metabolism*
  • Tumor Suppressor Proteins / chemistry
  • Tumor Suppressor Proteins / metabolism

Substances

  • Escherichia coli Proteins
  • HOPX protein, human
  • HSP90 Heat-Shock Proteins
  • Homeodomain Proteins
  • Peptides
  • Proteins
  • Tumor Suppressor Proteins