Super-motifs and evolution of tandem leucine-rich repeats within the smallproteoglycans - Biglycan, decorin, lumican, fibromodulin, PRELP, keratocan, osteoadherin, epiphycan, and osteoglycin

Leucine-rich repeats (LRRs) with 20-30 amino acids in unit length are prese nt in many proteins from prokaryotes to eukaryotes, The LRR-containing prot eins include a family of nine small proteoglycans, forming three distinct s ubfamilies: class I contains biglycan/PG-I and decorin/PG-II; class II: lum ican, fibromodulin, PRELP, keratocan, and osteoadherin; and class III: epip hycan/PG-Lb and osteoglycin or osteoinductive factor. Comparative sequence analysis of the 34 available protein sequences reveals that these proteogly cans have two types of LRRs, which we call S and T. The type S LRR is 21 re sidues long and has the consensus sequence of xxaPzxLPxxLxLxxNxI. The type T LRR has 26 residues; its consensus sequence is zzxxaxxxxFxxaxxLxxLxLxxNxL .. In both "x" indicates variable residue; "z" is frequently a gap; "a" is Val, Leu, or ne; and I is ne or Leu. These type S and T LRRs are ordered in to two super-motifs-STT with about 73 residues in classes I and II and ST w ith about 47 residues in class III. The 12 LRRs in the small proteoglycans of I and II are best represented as (STT)(4); the seven LRRs of class III a s (ST)T(ST)(2). Our analyses indicate that classes I/II and III evolved alo ng different paths after the establishment of the precursor ST, and classes I and II also diverged after the establishment of the precursor (STT)(4). Proteins 2000;38:210-225. (C) 2000 Wiley-Liss, Inc.