Design of stable alpha-helical arrays from an idealized TPR motif.
The tetratricopeptide repeat (TPR) is a 34-amino acid alpha-helical motif that occurs in over 300 different proteins. In the different proteins, three to sixteen or more TPR motifs occur in tandem arrays and function to mediate protein-protein interactions. The binding specificity of each TPR protein is different, although the underlying structural motif is the same. Here we describe a statistical approach to the design of an idealized TPR motif. We present the high-resolution X-ray crystal structures (to 1.55 and 1.6 A) of designed TPR proteins and describe their solution properties and stability. A detailed analysis of these structures provides an understanding of the TPR motif, how it is repeated to give helical arrays with different superhelical twists, and how a very stable framework may be constructed for future functional designs.
Main
Ewan R G
ER
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Xiong
Yong
Y
Cocco
Melanie J
MJ
D'Andrea
Luca
L
Regan
Lynne
L
D020816:Amino Acid Motifs; D000818:Animals; D016384:Consensus Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015202:Protein Engineering; D017433:Protein Structure, Secondary