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, res ...
structural motif 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 ...
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, ...
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
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 ge ...
-
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 ...
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
* ...
, 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 n ...
residues. The region between the helices and sheets is the protein's
hydrophobic core and is tightly
steric
Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...
ally 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 prot ...
, 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 ...
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 single-pass membrane-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize ...
also share the motif. In fact, 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 single-pass membrane-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize ...
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.
Associated domains
Leucine-rich repeats are often flanked by
N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
and
C-terminal cysteine
Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile.
When present as a deprotonated catalytic residue, some ...
-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
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 ge ...
domains, which have been
structurally described for the protein
Internalin (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 am ...
''
Listeria 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.
An
iron sulphur cluster is found at the N-terminus of some
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, res ...
s containing the leucine-rich repeat variant domain (LRV). These
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, res ...
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 ...
, but does not appear to have reversible
redox
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or ...
activity.
See also
*
Leucine zipper
References
Further reading
*
*
External links
*
SCOP LRR foldCATH Alpha-beta horseshoe architectureLRRML: a conformational database of leucine-rich repeats
{{InterPro content, IPR004830
LRR proteins
Protein families