title: Protein design to understand peptide ligand recognition by tetratricopeptide repeat proteins.
abstract: Protein design aims to understand the fundamentals of protein structure by creating novel proteins with pre-specified folds. An equally important goal is to understand protein function by creating novel proteins with pre-specified activities. Here we describe the design and characterization of a tetratricopeptide (TPR) protein, which binds to the C-terminal peptide of the eukaryotic chaperone Hsp90. The design emphasizes the importance of both direct, short-range protein-peptide interactions and of long-range electrostatic optimization. We demonstrate that the designed protein binds specifically to the desired peptide and discriminates between it and the similar C-terminal peptide of Hsp70.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, PO Box 208114, New Haven, CT 06520-8114, USA.
authors.forename: Aitziber L
authors.initials: AL
authors.lastname: Cortajarena
authors.forename: Tommi
authors.initials: T
authors.lastname: Kajander
authors.forename: Weilan
authors.initials: W
authors.lastname: Pan
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Cocco
authors.forename: Lynne
authors.initials: L
authors.lastname: Regan
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D008024:Ligands; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
chemical_list: D018841:HSP90 Heat-Shock Proteins; D008024:Ligands; D010455:Peptides