Functional diversity of ankyrin repeats in microbial proteins

Abstract

The ankyrin repeat (ANK) is the most common protein-protein interaction motif in nature, and is predominantly found in eukaryotic proteins. Genome sequencing of various pathogenic or symbiotic bacteria and eukaryotic viruses has identified numerous genes encoding ANK-containing proteins that are proposed to have been acquired from eukaryotes by horizontal gene transfer. However, the recent discovery of additional ANK-containing proteins encoded in the genomes of archaea and free-living bacteria suggests either a more ancient origin of the ANK motif or multiple convergent evolution events. Many bacterial pathogens employ various types of secretion systems to deliver ANK-containing proteins into eukaryotic cells, where they mimic or manipulate various host functions. Studying the molecular and biochemical functions of this family of proteins will enhance our understanding of important host-microbe interactions.

Figure 1

Conserved structural features of the ANK motif. (a) Two ANK consensus sequences, derived mostly from eukaryotic proteins (i, ii) [2, 14] are compared to a consensus sequence from bacterial proteins (iii). The bacterial consensus sequence was produced using Jalview (http://www.jalview.org/) by aligning 3845 ANK sequences obtained from the SMART database; secondary structure was confirmed by using the JPRED3 server (http://www.compbio.dundee.ac.uk/). Residues are colored using the CLUSTALW color scheme implemented in Jalview. The Kohl et al. [14] sequence includes an X that denotes any amino acid except C, G, and P and Z that can be a H, N or Y. (b, c) An ANK repeat is composed of two α-helices arranged in an antiparallel fashion, and a β-loop that projects outward at an approximately 90° angle to facilitate the formation of hairpin-like β-sheets with neighboring loops. Panel (c) shows the crystal structure of ANK repeats for the cell cycle regulator Swi6 from yeast, reproduced from Ref. [4] with permission.

Figure 2

Distribution of ANK-containing proteins among different organisms. (a) Genes encoding ANK-containing proteins are found in the genomes of eukaryotes (where they are ubiquitous), eukaryotic viruses, bacteria and archaea. The number (N) of these proteins seems to increase with increasing phenotypic complexity among eukaryotes (compare Caenorhabditis elegans, Drosophila, mouse and human). Differences in biological complexity among eukaryotes and bacteria might explain why ANK-24 containing proteins appear to be underrepresented among bacterial genomes (Box 2). (b) ANK-containing proteins in bacteria (only groups with N ≥ 20 are shown). These analyses were performed with Interpro ver 18.0 [11] and Pfam ver 23.0 [9].