Insights into the evolution of extracellular leucine-rich repeats in metazoans with special reference to Toll-like receptor 4

ABSTRACT

The importance of the widely spread leucine-rich repeat (LRR) motif was studied considering TLRs, the LRR-containingprotein involved in animal immune response. The protein connects intracellular signalling with a chain of molecularinteractions through the presence of LRRs in the ectodomain and TIR in the endodomain. Domain analyses with humanTLR1-9 reported ectodomain with tandem repeats, transmembrane domain and TIR domain. The repeat number variedacross members of TLR and remained characteristic to a particular member. Analysis of gene structure revealed absence ofcodon interruption with TLR3 and TLR4 as exceptions. Extensive study with TLR4 from metazoans confirmed thepresence of 23 LRRs in tandem. Distinct clade formation using coding and amino acid sequence of individual repeatsillustrated independent evolution. Although ectodomain and endodomain exhibited differential selection pressure, withinthe ectodomain, however, the individual repeats displayed positive, negative and neutral selection pressure depending ontheir structural and functional significance.