A leucine-rich repeat (LRR) is a
proteinstructural motif that forms an α/β horseshoefold.[1][2] It is composed of repeating 20–30
amino acid stretches that are unusually rich in the
hydrophobic amino acid
leucine. These
tandem repeats commonly fold together to form a
solenoid protein domain, termed leucine-rich repeat domain. Typically, each repeat unit has
beta strand-
turn-
alpha helix structure, and the assembled
domain, composed of many such repeats, has a horseshoe shape with an interior parallel beta sheet and an exterior array of helices. One face of the beta sheet and one side of the helix array are exposed to
solvent and are therefore dominated by
hydrophilic residues. The region between the helices and sheets is the protein's
hydrophobic core and is tightly
sterically packed with leucine residues.
Leucine-rich repeat motifs have been identified in a large number of functionally unrelated proteins.[5] The best-known example is the
ribonuclease inhibitor, but other proteins such as the
tropomyosin regulator
tropomodulin and the
toll-like receptor also share the motif. In fact, the
toll-like receptor possesses 10 successive LRR motifs which serve to bind pathogen- and danger-associated molecular patterns.
Although the canonical LRR protein contains approximately one helix for every beta strand, variants that form
beta-alpha superhelix folds sometimes have long loops rather than helices linking successive beta strands.
One leucine-rich repeat variant domain (LRV) has a novel repetitive
structural motif consisting of alternating alpha- and
310-helices arranged in a right-handed superhelix, with the absence of the
beta-sheets present in other leucine-rich repeats.[6]
They also co-occur with LRR adjacent domains. These are small, all
beta strand domains, which have been
structurally described for the protein
Internalin (InlA) and related proteins InlB, InlE, InlH from the
pathogenicbacteriumListeria monocytogenes. Their function appears to be mainly structural: They are fused to the C-terminal end of leucine-rich repeats, significantly stabilising the LRR, and forming a common rigid entity with the LRR. They are themselves not involved in
protein-protein-interactions but help to present the adjacent LRR-domain for this purpose. These
domains belong to the family of
Ig-like domains in that they consist of two sandwiched
beta sheets that follow the classical connectivity of Ig-domains. The beta strands in one of the
sheets is, however, much smaller than in most standard Ig-like domains, making it somewhat of an outlier.[7][8][9]
An
iron sulphur cluster is found at the N-terminus of some
proteins containing the leucine-rich repeat variant domain (LRV). These
proteins have a two-domain structure, composed of a small N-terminal domain containing a cluster of four Cysteine residues that houses the
4Fe:4S cluster, and a larger C-terminal domain containing the LRV repeats.[6]Biochemical studies revealed that the 4Fe:4S cluster is sensitive to
oxygen, but does not appear to have reversible
redox activity.
^Enkhbayar P, Kamiya M, Osaki M, Matsumoto T, Matsushima N (February 2004). "Structural principles of leucine-rich repeat (LRR) proteins". Proteins. 54 (3): 394–403.
doi:
10.1002/prot.10605.
PMID14747988.
S2CID19951452.
^Kobe B, Kajava AV (December 2001). "The leucine-rich repeat as a protein recognition motif". Curr. Opin. Struct. Biol. 11 (6): 725–32.
doi:
10.1016/S0959-440X(01)00266-4.
PMID11751054.
^
abPeters JW, Stowell MH, Rees DC (December 1996). "A leucine-rich repeat variant with a novel repetitive protein structural motif". Nat. Struct. Biol. 3 (12): 991–4.
doi:
10.1038/nsb1296-991.
PMID8946850.
S2CID36535731.
^Schubert WD, Gobel G, Diepholz M, Darji A, Kloer D, Hain T, Chakraborty T, Wehland J, Domann E, Heinz DW (September 2001). "Internalins from the human pathogen Listeria monocytogenes combine three distinct folds into a contiguous internalin domain". J. Mol. Biol. 312 (4): 783–94.
doi:
10.1006/jmbi.2001.4989.
PMID11575932.
^Freiberg A, Machner MP, Pfeil W, Schubert WD, Heinz DW, Seckler R (March 2004). "Folding and stability of the leucine-rich repeat domain of internalin B from Listeri monocytogenes". J. Mol. Biol. 337 (2): 453–61.
doi:
10.1016/j.jmb.2004.01.044.
PMID15003459.
Further reading
Tooze, John; Brändén, Carl-Ivar (1999). Introduction to Protein Structure (2nd ed.). New York: Garland Publishing.
ISBN0-8153-2305-0.