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
[3][2].
Various crystallographic studies of leucine-rich repeats revealed that each
LRR contains a beta-strand and an alpha-helix connected by loops (see for
example {PDB:2BNH})
[5]. Multiple LRRs are arranged so that they form a
nonglobular, horseshoe-shaped structure, wherein parallel beta-sheets line the
inner circumference of the horseshoe (the concave side) and alpha-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
[1][4].
The profile we developed covers the 22 amino acids of the LRR repeat.