Metazoan evolution of the armadillo repeat superfamily

Abstract

The superfamily of armadillo repeat proteins is a fascinating archetype of modular-binding proteins involved in various fundamental cellular processes, including cell-cell adhesion, cytoskeletal organization, nuclear import, and molecular signaling. Despite their diverse functions, they all share tandem armadillo (ARM) repeats, which stack together to form a conserved three-dimensional structure. This superhelical armadillo structure enables them to interact with distinct partners by wrapping around them. Despite the important functional roles of this superfamily, a comprehensive analysis of the composition, classification, and phylogeny of this protein superfamily has not been reported. Furthermore, relatively little is known about a subset of ARM proteins, and some of the current annotations of armadillo repeats are incomplete or incorrect, often due to high similarity with HEAT repeats. We identified the entire armadillo repeat superfamily repertoire in the human genome, annotated each armadillo repeat, and performed an extensive evolutionary analysis of the armadillo repeat proteins in both metazoan and premetazoan species. Phylogenetic analyses of the superfamily classified them into several discrete branches with members showing significant sequence homology, and often also related functions. Interestingly, the phylogenetic structure of the superfamily revealed that about 30 % of the members predate metazoans and represent an ancient subset, which is gradually evolving to acquire complex and highly diverse functions.

Structure of the nucleation‐promoting factorSPIN90 bound to the actin filament nucleator Arp2/3 complex

“…Much of the interaction surface for SPIN90 on Arp2/3 complex is also conserved (Fig EV2; Beltzner & Pollard, ). We note that the interaction between SPIN90 ARM domain and Arp2/3 complex is distinct from other ARM domains, which typically use their concave surface to accommodate extended polypeptides (Gul et al , ).…”

Genome-wide discovery, and computational and transcriptional characterization of an AIG gene family in the freshwater snail Biomphalaria glabrata, a vector for Schistosoma mansoni

“…Other specialized domains associated with the B. glabrata AIG1 domain include death domain superfamily members [40,41], caspase activation and recruitment (CARD) domains [42,43], and a protein kinase domain for a B. glabrata GIMAP (the latter also known from Atlantic salmon (Salmo salar) or fungi). Also found were Armadillo-type fold domains possibly facilitating large molecule (protein or nucleic acids) binding capability [44,45] and a Hint domain associated with proteolysis functions [46].…”

Curvature of designed armadillo repeat proteins allows modular peptide binding

“…The name derives from the appearance of a Drosophila mutant with a defect in a segment polarity gene later identified as β-catenin (Nüsslein-Volhard and Wieschaus, 1980). Natural armadillo repeat proteins (nArmRP) are abundant in the human genome and usually consist of 4-12 consecutive repeats (Gul et al, 2016) where the repeats at either terminus (called N-and C-cap, respectively) are modified to protect the hydrophobic core from solvent exposure. Each repeat is usually made from 42 residues that fold into three triangularly arranged helices (H1, H2 and H3), and the angular stacking of several repeats creates a binding groove of adjacent H3 helices (Huber et al, 1997).…”