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Structures of designed armadillo‐repeat proteins show propagation of inter‐repeat interface effects
Author(s) -
Reichen Christian,
Madhurantakam Chaithanya,
Hansen Simon,
Grütter Markus G.,
Plückthun Andreas,
Mittl Peer R. E.
Publication year - 2016
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.374
H-Index - 138
ISSN - 2059-7983
DOI - 10.1107/s2059798315023116
Subject(s) - armadillo , biology , modularity (biology) , computational biology , modular design , genetics , microbiology and biotechnology , computer science , operating system
The armadillo repeat serves as a scaffold for the development of modular peptide‐recognition modules. In order to develop such a system, three crystal structures of designed armadillo‐repeat proteins with third‐generation N‐caps (Y III ‐type), four or five internal repeats (M‐type) and second‐generation C‐caps (A II ‐type) were determined at 1.8 Å (His‐Y III M 4 A II ), 2.0 Å (His‐Y III M 5 A II ) and 1.95 Å (Y III M 5 A II ) resolution and compared with those of variants with third‐generation C‐caps. All constructs are full consensus designs in which the internal repeats have exactly the same sequence, and hence identical conformations of the internal repeats are expected. The N‐cap and internal repeats M 1 to M 3 are indeed extremely similar, but the comparison reveals structural differences in internal repeats M 4 and M 5 and the C‐cap. These differences are caused by long‐range effects of the C‐cap, contacting molecules in the crystal, and the intrinsic design of the repeat. Unfortunately, the rigid‐body movement of the C‐terminal part impairs the regular arrangement of internal repeats that forms the putative peptide‐binding site. The second‐generation C‐cap improves the packing of buried residues and thereby the stability of the protein. These considerations are useful for future improvements of an armadillo‐repeat‐based peptide‐recognition system.