PROSITE documentation PDOC51450

Leucine rich repeat profile

The leucine-rich repeat (LRR) domain is formed from tandem arrays (2 to 52 repeats) containing a leucine-rich consensus sequence. LRR proteins have been identified in viruses, bacteria, archae and eukaryotes. LRR domains mediate macromolecular interactions in processes as diverse as bacterial invasion of host cells, the plant immune response, and inhibition of RNA binding. All LRR repeats can be divided into a highly conserved segment and a variable segment. The highly conserved segment consists either of an 11-residue stretch, LxxLxLxxNxL, or a 12-residue stretch, LxxLxLxxCxxL. Variable sequences connecting the consensus provide functional diversity for binding [1,2].

Various crystallographic studies of leucine-rich repeats revealed that each LRR contains a β-strand and an α-helix connected by loops (see for example <PDB:2BNH>) [3]. Multiple LRRs are arranged so that they form a nonglobular, horseshoe-shaped structure, wherein parallel β-sheets line the inner circumference of the horseshoe (the concave side) and α-helices decorate the outer circumference (the convex side). Although the sequences and numbers of LRRs can differ, diverse LRRs share this overall horseshoe shape. Mutagenesis studies and structural analyses of LRR-ligand complexes have revealed that the concave surface of LRRs is involved mainly in ligand binding [2].

In various types of repeats it has been shown that they fold in a highly cooperative manner. In general folding of an individual repeat is energetically unfavorable, whereas formation of interrepeat interfaces is highly favorable. Thus, folding is initiated only when two adjacent repeats fold forming a favorable interface. Once this activation energy barrier is surpassed, folding proceeds rapidly, via a nucleation-propagation mechanism. In some LRR repeats it has been show that nucleation initiate in the N-terminal capping domain [4,5].

The profile we developed covers the 22 amino acids of the LRR repeat.