A leucine-rich repeat (LRR) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

structural motif In a polymer, chain-like biological molecule, such as a protein or nucleic acid, a structural motif is a common Biomolecular structure#Tertiary structure, three-dimensional structure that appears in a variety of different, evolutionarily unrel ...

that forms an α/β horseshoe fold. It is composed of repeating 20–30

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

stretches that are unusually rich in the

hydrophobic In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, t ...

amino acid

leucine Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α- ca ...

. These

tandem repeats Tandem repeats occur in DNA when a pattern of one or more nucleotides is repeated and the repetitions are directly adjacent to each other. Several protein domains also form tandem repeats within their amino acid primary structure, such as armadil ...

commonly fold together to form a

solenoid protein domain Solenoid protein domains are a highly modular type of protein domain. They consist of a chain of nearly identical folds, often simply called tandem repeats. They are extremely common among all types of proteins, though exact figures are unknown. ...

, termed leucine-rich repeat domain. Typically, each repeat unit has

beta strand The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a g ...

- turn-

alpha helix The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues e ...

structure, and the assembled

domain Domain may refer to: Mathematics *Domain of a function, the set of input values for which the (total) function is defined **Domain of definition of a partial function **Natural domain of a partial function **Domain of holomorphy of a function * Do ...

, 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 A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...

and are therefore dominated by

hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are ...

residues. The region between the helices and sheets is the protein's

hydrophobic core The hydrophobic effect is the observed tendency of nonpolar substances to aggregate in an aqueous solution and exclude water molecules. The word hydrophobic literally means "water-fearing", and it describes the segregation of water and nonpolar ...

and is tightly sterically packed with leucine residues. Leucine-rich repeats are frequently involved in the formation of protein–protein interactions.

Examples

Leucine-rich repeat motifs have been identified in a large number of functionally unrelated proteins. The best-known example is the

ribonuclease inhibitor Ribonuclease inhibitor (RI) is a large (~450 residues, ~49 kDa), acidic (pI ~4.7), leucine-rich repeat protein that forms extremely tight complexes with certain ribonucleases. It is a major cellular protein, comprising ~0.1% of all cellular pr ...

, but other proteins such as the

tropomyosin Tropomyosin is a two-stranded alpha-helical, coiled coil protein found in actin-based cytoskeletons. Tropomyosin and the actin skeleton All organisms contain organelles that provide physical integrity to their cells. These type of organelles a ...

regulator tropomodulin and the

toll-like receptor Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are Bitopic protein, single-pass membrane-spanning Receptor (biochemistry), receptors usually expressed on sentinel cells such as macrophage ...

also share the motif. In fact, the

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

consisting of alternating alpha- and 3₁₀-helices arranged in a right-handed superhelix, with the absence of the

beta-sheet The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a g ...

s present in other leucine-rich repeats.

Associated domains

Leucine-rich repeats are often flanked by N-terminal and

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

cysteine-rich domains, but not always as is the case with

C5orf36 KIAA0825 is a protein that in humans is encoded by the gene of the same name, located on chromosome 5, 5q15. It is a possible risk factor in Type II Diabetes, and associated with high levels of glucose in the blood. It is a relatively fast mutati ...

They also co-occur with LRR adjacent domains. These are small, all

domains, which have been

structurally A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

described for the protein

Internalin Internalins are surface proteins found on ''Listeria monocytogenes''. They exist in two known forms, InlA and InlB. They are used by the bacteria to invade mammalian cells via cadherins transmembrane proteins and Met receptors respectively. The ex ...

(InlA) and related proteins InlB, InlE, InlH from the pathogenic

bacterium Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

Listeria monocytogenes ''Listeria monocytogenes'' is the species of pathogenic bacteria that causes the infection listeriosis. It is a facultative anaerobic bacterium, capable of surviving in the presence or absence of oxygen. It can grow and reproduce inside the host' ...

''. 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 The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gen ...

that follow the classical connectivity of Ig-domains. The beta strands in one of the

sheets A bed sheet is a rectangular piece of cloth used either singly or in a pair as bedding, which is larger in length and width than a mattress, and which is placed immediately above a mattress or bed, but below blankets and other bedding (such as ...

is, however, much smaller than in most standard Ig-like domains, making it somewhat of an outlier. An iron sulphur cluster is found at the N-terminus of some

s containing the leucine-rich repeat variant domain (LRV). These

s 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.

Biochemical Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology an ...

studies revealed that the 4Fe:4S cluster is sensitive to

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...

, but does not appear to have reversible

redox Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate (chemistry), substrate change. Oxidation is the loss of Electron, electrons or an increase in the oxidation state, while reduction ...

activity.

References

External links

*
SCOP LRR fold

CATH Alpha-beta horseshoe architecture

LRRML: a conformational database of leucine-rich repeats
{{InterPro content, IPR004830 LRR proteins Protein families

Examples

Associated domains

See also

References

Further reading

External links