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J Mol Biol. 2013 May 27;425(10):1826-1838. doi: 10.1016/j.jmb.2013.02.013. Epub 2013 Feb 19.

All repeats are not equal: a module-based approach to guide repeat protein design.

Sawyer N#1,2, Chen J#1,3, Regan L1,2,3,4.

Author information

1
Integrated Graduate Program in Physical and Engineering Biology, Yale University, 266 Whitney Avenue, New Haven, CT 06511, USA.
2
Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06511, USA.
3
Program in Computational Biology and Bioinformatics, Yale University, 266 Whitney Avenue, New Haven, CT 06511, USA.
4
Department of Chemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06511, USA.
#
Contributed equally

Abstract

Repeat proteins composed of tandem arrays of a short structural motif often mediate protein-protein interactions. Past efforts to design repeat protein-based molecular recognition tools have focused on the creation of templates from the consensus of individual repeats, regardless of their natural context. Such an approach assumes that all repeats are essentially equivalent. In this study, we present the results of a "module-based" approach in which modules composed of tandem repeats are aligned to identify repeat-specific features. Using this approach to analyze tetratricopeptide repeat modules that contain three tandem repeats (3TPRs), we identify two classes of 3TPR modules with distinct structural signatures that are correlated with different sets of functional residues. Our analyses also reveal a high degree of correlation between positions across the entire ligand-binding surface, indicative of a coordinated, coevolving binding surface. Extension of our analyses to different repeat protein modules reveals more examples of repeat-specific features, especially in armadillo repeat modules. In summary, the module-based analyses that we present effectively capture key repeat-specific features that will be important to include in future repeat protein design templates.

PMID:
23434848
PMCID:
PMC3928981
DOI:
10.1016/j.jmb.2013.02.013
[Indexed for MEDLINE]
Free PMC Article

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