LRRCT

Leucine rich repeat C-terminal domain

• SMART accession number: SM00082
• Interpro abstract (IPR000483):

  Leucine-rich repeats (LRR, see IPR001611) consist of 2-45 motifs of 20-30 amino acids in length that generally folds into an arc or horseshoe shape [(PUBMED:14747988)]. LRRs occur in proteins ranging from viruses to eukaryotes, and appear to provide a structural framework for the formation of protein-protein interactions [(PUBMED:11751054)]. Proteins containing LRRs include tyrosine kinase receptors, cell-adhesion molecules, virulence factors, and extracellular matrix-binding glycoproteins, and are involved in a variety of biological processes, including signal transduction, cell adhesion, DNA repair, recombination, transcription, RNA processing, disease resistance, apoptosis, and the immune response.

  LRRs are often flanked by cysteine-rich domains: an N-terminal LRR domain (IPR000372) and a C-terminal LRR domain. This entry represents the C-terminal LRR domain.

There are 4614 LRRCT domains in 3970 proteins in SMART's nrdb database.

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Kobe B, Deisenhofer J
• A structural basis of the interactions between leucine-rich repeats and protein ligands.
• Nature. 1995; 374: 183-6

The leucine-rich repeat is a recently characterized structural motif used in molecular recognition processes as diverse as signal transduction, cell adhesion, cell development, DNA repair and RNA processing. We present here the crystal structure at 2.5 A resolution of the complex between ribonuclease A and ribonuclease inhibitor, a protein built entirely of leucine-rich repeats. The unusual non-globular structure of ribonuclease inhibitor, its solvent-exposed parallel beta-sheet and the conformational flexibility of the structure are used in the interaction; they appear to be the principal reasons for the effectiveness of leucine-rich repeats as protein-binding motifs. The structure can serve as a model for the interactions of other proteins containing leucine-rich repeats with their ligands.

• Kobe B, Deisenhofer J
• The leucine-rich repeat: a versatile binding motif.
• Trends Biochem Sci. 1994; 19: 415-21

Leucine-rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations. All proteins containing these repeats are thought to be involved in protein-protein interactions. The crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to beta-alpha structural units. These units are arranged so that they form a parallel beta-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglobular shape. These two features may be responsible for the protein-binding functions of proteins containing leucine-rich repeats.

Disease (disease genes where sequence variants are found in this domain)

SwissProt sequences and OMIM curated human diseases associated with missense mutations within the LRRCT domain.

Protein	Disease
Glycocalicin (P07359) (SMART)	OMIM:231200: Bernard-Soulier syndrome

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
36.42	map04620	Toll-like receptor signaling pathway
16.18	map04512	ECM-receptor interaction
13.29	map04360	Axon guidance
12.14	map04640	Hematopoietic cell lineage
6.94	map04010	MAPK signaling pathway
4.05	map04510	Focal adhesion
2.89	map05216	Thyroid cancer
2.89	map04210	Apoptosis
1.73	map00680	Methane metabolism
1.73	map00940	Phenylpropanoid biosynthesis
1.73	map00360	Phenylalanine metabolism

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with LRRCT domain which could be assigned to a KEGG orthologous group, and not all proteins containing LRRCT domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of LRRCT domains in PDB

PDB code	Title
1gwb	Structure of glycoprotein 1b
1m0z	Crystal structure of the von willebrand factor binding domain of glycoprotein ib alpha
1m10	Crystal structure of the complex of glycoprotein ib alpha and the von willebrand factor a1 domain
1ook	Crystal structure of the complex of platelet receptor gpib- alpha and human alpha-thrombin
1ozn	1.5a crystal structure of the nogo receptor ligand binding domain reveals a convergent recognition scaffold mediating inhibition of myelination
1p8t	Crystal structure of nogo-66 receptor
1p8v	Crystal structure of the complex of platelet receptor gpib- alpha and alpha-thrombin at 2.6a
1p9a	Crystal structure of n-terminal domain of human platelet receptor glycoprotein ib-alpha at 1.7 angstrom resolution
1qyy	Crystal structure of n-terminal domain of human platelet receptor glycoprotein ib-alpha at 2.8 angstrom resolution
1sq0	Crystal structure of the complex of the wild-type von willebrand factor a1 domain and glycoprotein ib alpha at 2.6 angstrom resolution
1u0n	The ternary von willebrand factor a1-glycoprotein ibalpha- botrocetin complex
1w8a	Third lrr domain of drosophila slit
1ziw	Human toll-like receptor 3 extracellular domain structure
2a0z	The molecular structure of toll-like receptor 3 ligand binding domain
2id5	Crystal structure of the lingo-1 ectodomain
2ifg	Structure of the extracellular segment of human trka in complex with nerve growth factor
2o6q	Structural diversity of the hagfish variable lymphocyte receptors a29
2o6r	Structural diversity of the hagfish variable lymphocyte receptors b61
2o6s	Structural diversity of the hagfish variable lymphocyte receptors b59
2r9u	Crystal structure of lamprey variable lymphocyte receptor ectodomain
2v70	Third lrr domain of human slit2
2v9s	Second lrr domain of human slit2
2v9t	Complex between the second lrr domain of slit2 and the first ig domain from robo1
2wfh	The human slit 2 dimerization domain d4
2z62	Crystal structure of the tv3 hybrid of human tlr4 and hagfish vlrb.61
2z63	Crystal structure of the tv8 hybrid of human tlr4 and hagfish vlrb.61
2z64	Crystal structure of mouse tlr4 and mouse md-2 complex
2z65	Crystal structure of the human tlr4 tv3 hybrid-md-2- eritoran complex
2z66	Crystal structure of the vt3 hybrid of human tlr4 and hagfish vlrb.61
2z7x	Crystal structure of the tlr1-tlr2 heterodimer induced by binding of a tri-acylated lipopeptide
2z80	Crystal structure of the tlr1-tlr2 heterodimer induced by binding of a tri-acylated lipopeptide
2z81	Crystal structure of the tlr1-tlr2 heterodimer induced by binding of a tri-acylated lipopeptide
2z82	Crystal structure of the tlr1-tlr2 heterodimer induced by binding of a tri-acylated lipopeptide
3a79	Crystal structure of tlr2-tlr6-pam2csk4 complex
3a7b	Crystal structure of tlr2-streptococcus pneumoniae lipoteichoic acid complex
3a7c	Crystal structure of tlr2-pe-dtpa complex
3cig	Crystal structure of mouse tlr3 ectodomain
3ciy	Mouse toll-like receptor 3 ectodomain complexed with double- stranded rna
3e6j	Crystal structure of variable lymphocyte receptor (vlr) rbc36 in complex with h-trisaccharide
3fxi	Crystal structure of the human tlr4-human md-2-e.coli lps ra complex
3g39	Structure of a lamprey variable lymphocyte receptor
3g3a	Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen

Links (links to other resources describing this domain)

• INTERPRO: IPR000483