Keywords: Crystal Structure, Protein Design, Tetratricopeptide Repeat (tpr), Peptide Derivative, Unclassified Drug, Alpha Helix, Article, Priority Journal, Protein Motif, Protein Stability, Statistical Analysis, Structure Analysis, X Ray Analysis, Amino Acid Motifs, Animals, Consensus Sequence, Crystallography, X-Ray, Humans, Magnetic Resonance Spectroscopy, Protein Engineering, Protein Structure, Secondary,
Affiliations: *** IBB - CNR ***
Dept. of Molec. Biophys./Biochem., Yale University, New Haven, CT 06520, United States
Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, United States
Department of Chemistry, Yale University, New Haven, CT 06520, United States
Cambridge Univ. Chemical Laboratory, Cambridge University, Lensfield Road, Cambridge, CB2 1EW, United Kingdom
Inst. Biocrystallography/Bioimaging, Consiglio Nazionale delle Riecerche, Naples, Italy
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Gill, S. C., Von Hippel, P. H., Calculation of protein extinction coefficients from amino acid sequence data (1989) Anal. Biochem., 182, pp. 319-326
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Goddard, T. D., Kneller, D. G., SPARKY 3, , San Francisco: University of California, San Francisco
Kleywegt, G. J., Experimental assessment of differences between related protein crystal structures (1999) Acta Crystallogr. D Biol. Crystallogr., 55, pp. 1878-1884
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Murshudov, G. N., Vagin, A. A., Dodson, E. J., Refinement of macromolecular structures by the maximum-likelihood method (1997) Acta Crystallogr. D Biol. Crystallogr., 53, pp. 240-255
Christopher, J. A., Baldwin, T. O., Spock: Real-time collaborative molecular modeling (1998) J. Mol. Graph. Model., 16, p. 285
Merritt, E. A., Murphy, M. E. P., Raster3D version 2. 0. A program for photorealistic molecular graphics (1994) Acta Crystallogr. D Biol. Crystallogr., 50, pp. 869-873
Hutchinson, E. G., Thornton, J. M., PROMOTIF - A program to identify and analyze structural motifs in proteins (1996) Protein Sci., 5, pp. 212-220
Design of stable α-helical arrays from an idealized TPR motif
The tetratricopeptide repeat (TPR) is a 34-amino acid α-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 Å) 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.
Design of stable α-helical arrays from an idealized TPR motif
Petraglia F, Singh AA, Carafa V, Nebbioso A, Conte M, Scisciola L, Valente S, Baldi A, Mandoli A, Petrizzi VB, Ingenito C, De Falco S, Cicatiello V, Apicella I, Janssen-megens EM, Kim B, Yi G, Logie C, Heath S, Ruvo M, Wierenga ATJ, Flicek P, Yaspo ML, Della Valle V, Bernard O, Tomassi S, Novellino E, Feoli A, Sbardella G, Gut I, Vellenga E, Stunnenberg HG, Mai A, Martens JHA, Altucci L * Combined HAT/EZH2 modulation leads to cancer-selective cell death(284 views) Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking), 2018 May 22; 9(39): 25630-25646. Impact Factor:5.008 ViewExport to BibTeXExport to EndNote