Research Article: Structures of designed armadillo-repeat proteins show propagation of inter-repeat interface effects

Date Published: January 01, 2016

Publisher: International Union of Crystallography

Author(s): Christian Reichen, Chaithanya Madhurantakam, Simon Hansen, Markus G. Grütter, Andreas Plückthun, Peer R. E. Mittl.


Designed armadillo-repeat proteins are promising scaffolds for modular peptide-recognition systems. The crystal structures of His-YIIIM4AII, His-YIIIM5AII and YIIIM5AII highlight structural heterogeneity in full-consensus designs and aid the improvement of future constructs.

Partial Text

For the design of artificial peptide-binding modules, scaffolds with modular architectures are highly suitable. In particular, the armadillo repeat reveals structural properties that facilitate the design of peptide-binding modules on a rational basis (Andrade et al., 2001 ▸; Kajander et al., 2006 ▸; Boersma & Plückthun, 2011 ▸; Reichen, Hansen et al., 2014 ▸). In natural armadillo-repeat proteins such as importin-α and β-catenin, each repeat comprises three α-helices that are assembled in a triangular spiral staircase arrangement. All repeats are fused into a single protein with an elongated hydrophobic core (Figs. 1 ▸a and 1 ▸b). They recognize their target peptides in extended β-sheet conformations with very regular binding topologies. The main chain of the peptide is bound in an antiparallel direction by conserved asparagine residues on the concave side of the armadillo-repeat protein (Huber et al., 1997 ▸; Conti et al., 1998 ▸; Kobe, 1999 ▸; Fontes et al., 2003 ▸). Differences exist in side-chain preferences because the importin-α and β-catenin subfamilies recognize peptides with positively and negatively charged side chains, respectively (Conti & Kuriyan, 2000 ▸; Ishiyama et al., 2010 ▸; Poy et al., 2001 ▸).




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