Abstract
BackgroundThe small leucine-rich repeat proteins and proteoglycans (SLRPs) form an important family of regulatory molecules that participate in many essential functions. They typically control the correct assembly of collagen fibrils, regulate mineral deposition in bone, and modulate the activity of potent cellular growth factors through many signalling cascades. SLRPs belong to the group of extracellular leucine-rich repeat proteins that are flanked at both ends by disulphide-bonded caps that protect the hydrophobic core of the terminal repeats. A capping motif specific to SLRPs has been recently described in the crystal structures of the core proteins of decorin and biglycan. This motif, designated as LRRCE, differs in both sequence and structure from other, more widespread leucine-rich capping motifs. To investigate if the LRRCE motif is a common structural feature found in other leucine-rich repeat proteins, we have defined characteristic sequence patterns and used them in genome-wide searches.ResultsThe LRRCE motif is a structural element exclusive to the main group of SLRPs. It appears to have evolved during early chordate evolution and is not found in protein sequences from non-chordate genomes. Our search has expanded the family of SLRPs to include new predicted protein sequences, mainly in fishes but with intriguing putative orthologs in mammals. The chromosomal locations of the newly predicted SLRP genes would support the large-scale genome or gene duplications that are thought to have occurred during vertebrate evolution. From this expanded list we describe a new class of SLRP sequences that could be representative of an ancestral SLRP gene.ConclusionGiven its exclusivity the LRRCE motif is a useful annotation tool for the identification and classification of new SLRP sequences in genome databases. The expanded list of members of the SLRP family offers interesting insights into early vertebrate evolution and suggests an early chordate evolutionary origin for the LRRCE capping motif.
Highlights
The small leucine-rich repeat proteins and proteoglycans (SLRPs) form an important family of regulatory molecules that participate in many essential functions
Using the LRRCE regular expression pattern, a total of 175 sequences were retrieved by ScanProsite from the UniProt database (Swiss-Prot release 55.1, TrEMBL release 38.1) [48]
The LRRCE regular expression pattern was accurate: all sequences in this UniProt set were of proteins with leucine-rich repeat (LRR) architecture and had a repeat structure that identified them as canonical SLRPs, with the LRR N-terminal capping motif (LRRNT) capping motif
Summary
The small leucine-rich repeat proteins and proteoglycans (SLRPs) form an important family of regulatory molecules that participate in many essential functions. The continuously expanding LRR superfamily includes intracellular, extracellular and membrane-attached proteins characterized by a common modular architecture specially suited to favour protein-protein interactions [13,5,7,8,9] These proteins participate in a variety of important biological functions, including among others cell adhesion and signalling, platelet aggregation, neural development, extracellular matrix assembly, bacterial pathogenicity, disease resistance and immune response [10,11,12,13,14,15,16,17,18,19,20]. Some LRR proteins have been shown to form highly stable dimers through their concave side [28,29,30,31] raising the possibility of alternative scenarios where LRR dimers are either the functional units or latent forms that require dissociation prior to ligand binding [32]
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