Protein design to understand peptide ligand recognition by tetratricopeptide repeat proteins.
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.
Cortajarena
Aitziber L
AL
Department of Molecular Biophysics and Biochemistry, Yale University, PO Box 208114, New Haven, CT 06520-8114, USA.
Kajander
Tommi
T
Pan
Weilan
W
Cocco
Melanie J
MJ
Regan
Lynne
L
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
D018841:HSP90 Heat-Shock Proteins; D008024:Ligands; D010455:Peptides