title: Design of Protein-Peptide Interaction Modules for Assembling Supramolecular Structures in Vivo and in Vitro.
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.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University , New Haven, Connecticut 06511, United States.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Speltz
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University , New Haven, Connecticut 06511, United States.
authors.forename: Aparna
authors.initials: A
authors.lastname: Nathan
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University , New Haven, Connecticut 06511, United States.|Department of Chemistry, Yale University , New Haven, Connecticut 06511, United States.|Integrated Graduate Program in Physical and Engineering Biology , New Haven, Connecticut 06511, United States.
authors.forename: Lynne
authors.initials: L
authors.lastname: Regan
mesh_terms: D000595:Amino Acid Sequence; D004926:Escherichia coli / Q000737:chemistry / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D057809:HEK293 Cells; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D060066:Protein Interaction Maps; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; C476884:HOPX protein, human; D018841:HSP90 Heat-Shock Proteins; D018398:Homeodomain Proteins; D010455:Peptides; D011506:Proteins; D025521:Tumor Suppressor Proteins