A structural view of the Ankyrin-repeat Proteoverse

PARRA RODRIGO GONZALO; ROCIO ESPADA; VERSTRAETE NINA; DIEGO ULISES FERREIRO

Sao Paulo

Simposio; Symposium on Current Topics in Molecular Biophysics; 2014; 2014

USP

Background: Natural protein sequences resemble random strings of amino acids. Patterns of a relatively small set of folding architectures can be characterized by long distance interactions among amino acids. Repeat proteins are composed of tandem copies of similar motifs and can get spontaneously organized in symmetrical ways in space. Ankyrin repeat proteins comprise a large number of proteins containing tandem copies of a ~33 residues length motif. They are present in all kingdoms of life, and are apparently enriched in eukaryotes and some specific pathogens. We have shown that some repeat proteins can appear nearly periodic, while in others clear separations between repetitions exist. Results: Here we show that the geometry itself is not enough to define a preferred phase for all natural Ankyrin-repeat arrays. When folding energetic parameters are included, a particular phase to define the ankyrin domains emerge. With this definition we annotated the location of the structural repeat occurrences on the molecules using only 3D structural information. The strategy allows for the identification of structural modifications such as insertions and deletions in the repeat array, and quantify how these perturb the overall symmetry of the repeat domain. We exhaustively analyzed the currently known ankyrin repeat structural space at the levels of individual repeats, the repetitive arrays, the whole molecules as well as the interactions with their structural partners in order to deconvolute how structural perturbations propagate in these systems and how are these reflected in their primary sequence.