A nested leucine rich repeat (LRR) domain: The precursor of LRRs is a ten or eleven residue motif

Background: Leucine rich repeats (LRRs) are present in over 60,000 proteins that have been identified in viruses, bacteria, archae, and eukaryotes. All known structures of repeated LRRs adopt an arc shape. Most LRRs are 20-30 residues long. All LRRs contain LxxLxLxxNxL, in which L is Leu, Ile, Val, or Phe and N is Asn, Thr, Ser, or Cys and x is any amino acid. Seven classes of LRRs have been identified. However, other LRR classes remains to be characterized. The evolution of LRRs is not well understood. Results: Here we describe a novel LRR domain, or nested repeat observed in 134 proteins from 54 bacterial species. This novel LRR domain has 21 residues with the consensus sequence of LxxLxLxxNxLxxLDLxx(N/L/Q/x)xx or LxxLxCxxNxLxxLDLxx(N/L/x)xx. This LRR domain is characterized by a nested periodicity; it consists of alternating 10- and 11-residues units of LxxLxLxxNx(x/-). We call it IRREKO LRR, since the Japanese word for nested is IRREKO. The first unit of the IRREKO LRR domain is frequently occupied by an SDS22-like LRR with the consensus of LxxLxLxxNxLxxLxxLxxLxx or a Bacterial LRR with the consensus of LxxLxLxxNxLxxLPxLPxx. In some proteins an SDS22-like LRR intervenes between IRREKO LRRs. Conclusion: Proteins having IRREKO LRR domain are almost exclusively found in bacteria. It is suggested that IRREKO@LRR evolved from a common ancestor with SDS22-like and Bacterial classes and that the ancestor of IRREKO@LRR is 10 or 11 residues of LxxLxLxxNx(x/-). The IRREKO LRR is predicted to adopt an arc shape with smaller curvature in which beta-strands are formed on both concave and convex surfaces.