Summary: LRR adjacent
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This is the Wikipedia entry entitled "Leucine-rich repeat". More...
Leucine-rich repeat Edit Wikipedia article
 An example of a leucine-rich repeat protein, a porcine ribonuclease inhibitor | |||||||||
| Identifiers | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Symbol | LRR_1 | ||||||||
| Pfam | PF00560 | ||||||||
| Pfam clan | CL0022 | ||||||||
| InterPro | IPR001611 | ||||||||
| SCOPe | 2bnh / SUPFAM | ||||||||
| Membranome | 605 | ||||||||
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| Leucine rich repeat variant | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 a leucine-rich repeat variant with a novel repetitive protein structural motif | |||||||||
| Identifiers | |||||||||
| Symbol | LRV | ||||||||
| Pfam | PF01816 | ||||||||
| Pfam clan | CL0020 | ||||||||
| InterPro | IPR004830 | ||||||||
| SCOPe | 1lrv / SUPFAM | ||||||||
| Membranome | 737 | ||||||||
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| LRR adjacent | |||||||||
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 internalin h: crystal structure of fused n-terminal domains. | |||||||||
| Identifiers | |||||||||
| Symbol | LRR_adjacent | ||||||||
| Pfam | PF08191 | ||||||||
| InterPro | IPR012569 | ||||||||
| Membranome | 341 | ||||||||
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| Leucine rich repeat N-terminal domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 dimeric bovine tissue-extracted decorin, crystal form 2 | |||||||||
| Identifiers | |||||||||
| Symbol | LRRNT | ||||||||
| Pfam | PF01462 | ||||||||
| InterPro | IPR000372 | ||||||||
| SMART | LRRNT | ||||||||
| SCOPe | 1m10 / SUPFAM | ||||||||
| Membranome | 127 | ||||||||
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| Leucine rich repeat N-terminal domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 the crystal structure of pgip (polygalacturonase inhibiting protein), a leucine rich repeat protein involved in plant defense | |||||||||
| Identifiers | |||||||||
| Symbol | LRRNT_2 | ||||||||
| Pfam | PF08263 | ||||||||
| InterPro | IPR013210 | ||||||||
| SMART | LRRNT | ||||||||
| SCOPe | 1m10 / SUPFAM | ||||||||
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| Leucine rich repeat C-terminal domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 third lrr domain of drosophila slit | |||||||||
| Identifiers | |||||||||
| Symbol | LRRCT | ||||||||
| Pfam | PF01463 | ||||||||
| InterPro | IPR000483 | ||||||||
| SMART | LRRCT | ||||||||
| SCOPe | 1m10 / SUPFAM | ||||||||
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| LRV protein FeS4 cluster | |||||||||
|---|---|---|---|---|---|---|---|---|---|
a leucine-rich repeat variant with a novel repetitive protein structural motif | |||||||||
| Identifiers | |||||||||
| Symbol | LRV_FeS | ||||||||
| Pfam | PF05484 | ||||||||
| Pfam clan | CL0020 | ||||||||
| InterPro | IPR008665 | ||||||||
| SCOPe | 1lrv / SUPFAM | ||||||||
| |||||||||
A leucine-rich repeat (LRR) is a protein structural motif that forms an α/β horseshoe fold.[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 repeats are frequently involved in the formation of protein–protein interactions.[3][4]
Contents
Examples
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]
Associated domains
Leucine-rich repeats are often flanked by N-terminal and C-terminal cysteine-rich domains, but not always as is the case with C5orf36
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 pathogenic bacterium 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.[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.
See also
References
- ^ Kobe B, Deisenhofer J (October 1994). "The leucine-rich repeat: a versatile binding motif". Trends Biochem. Sci. 19 (10): 415–21. doi:10.1016/0968-0004(94)90090-6. PMID 7817399.
- ^ 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. PMID 14747988.
- ^ 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. PMID 11751054.
- ^ Gay NJ, Packman LC, Weldon MA, Barna JC (October 1991). "A leucine-rich repeat peptide derived from the Drosophila Toll receptor forms extended filaments with a beta-sheet structure". FEBS Lett. 291 (1): 87–91. doi:10.1016/0014-5793(91)81110-T. PMID 1657640.
- ^ Rothberg JM, Jacobs JR, Goodman CS, Artavanis-Tsakonas S (December 1990). "slit: an extracellular protein necessary for development of midline glia and commissural axon pathways contains both EGF and LRR domains". Genes Dev. 4 (12A): 2169–87. doi:10.1101/gad.4.12a.2169. PMID 2176636.
- ^ a b Peters 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. PMID 8946850.
- ^ 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. PMID 11575932.
- ^ Schubert WD, Urbanke C, Ziehm T, Beier V, Machner MP, Domann E, Wehland J, Chakraborty T, Heinz DW (December 2002). "Structure of internalin, a major invasion protein of Listeria monocytogenes, in complex with its human receptor E-cadherin". Cell. 111 (6): 825–36. doi:10.1016/S0092-8674(02)01136-4. PMID 12526809.
- ^ 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. PMID 15003459.
Further reading
- Tooze, John; Brändén, Carl-Ivar (1999). Introduction to Protein Structure (2nd ed.). New York: Garland Publishing. ISBN 0-8153-2305-0.
- Wei T, Gong J, Jamitzky F, Heckl WM, Stark RW, Roessle SC (November 2008). "LRRML: a conformational database and an XML description of leucine-rich repeats (LRRs)". BMC Struct. Biol. 8 (1): 47. doi:10.1186/1472-6807-8-47. PMC 2645405. PMID 18986514.
External links
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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
LRR adjacent Provide feedback
These are small, all beta strand domains, structurally described for the protein Internalin (InlA) and related proteins InlB, InlE, InlH from the pathogenic bacterium Listeria monocytogenes. Their function appears to be mainly structural: They are fused to the C-terminal end of leucine-rich repeats (LRR), 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 [1] [3].
Literature references
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Schubert WD, Gobel G, Diepholz M, Darji A, Kloer D, Hain T, Chakraborty T, Wehland J, Domann E, Heinz DW; , J Mol Biol 2001;312:783-794.: Internalins from the human pathogen Listeria monocytogenes combine three distinct folds into a contiguous internalin domain. PUBMED:11575932 EPMC:11575932
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Schubert WD, Urbanke C, Ziehm T, Beier V, Machner MP, Domann E, Wehland J, Chakraborty T, Heinz DW; , Cell 2002;111:825-836.: Structure of internalin, a major invasion protein of Listeria monocytogenes, in complex with its human receptor E-cadherin. PUBMED:12526809 EPMC:12526809
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Freiberg A, Machner MP, Pfeil W, Schubert WD, Heinz DW, Seckler R; , J Mol Biol 2004;337:453-461.: Folding and stability of the leucine-rich repeat domain of internalin B from Listeri monocytogenes. PUBMED:15003459 EPMC:15003459
This tab holds annotation information from the InterPro database.
InterPro entry IPR012569
Leucine-rich repeats (LRR) 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, PUBMED:1657640].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 [PUBMED:2176636].
Sequence analyses of LRR proteins suggested the existence of several different subfamilies of LRRs. The significance of this classification is that repeats from different subfamilies never occur simultaneously and have most probably evolved independently. It is, however, now clear that all major classes of LRR have curved horseshoe structures with a parallel beta sheet on the concave side and mostly helical elements on the convex side. At least six families of LRR proteins, characterised by different lengths and consensus sequences of the repeats, have been identified. Eleven-residue segments of the LRRs (LxxLxLxxN/CxL), corresponding to the beta-strand and adjacent loop regions, are conserved in LRR proteins, whereas the remaining parts of the repeats (herein termed variable) may be very different. Despite the differences, each of the variable parts contains two half-turns at both ends and a "linear" segment (as the chain follows a linear path overall), usually formed by a helix, in the middle. The concave face and the adjacent loops are the most common protein interaction surfaces on LRR proteins. 3D structure of some LRR proteins-ligand complexes show that the concave surface of LRR domain is ideal for interaction with alpha-helix, thus supporting earlier conclusions that the elongated and curved LRR structure provides an outstanding framework for achieving diverse protein-protein interactions [PUBMED:11751054]. Molecular modeling suggests that the conserved pattern LxxLxL, which is shorter than the previously proposed LxxLxLxxN/CxL is sufficient to impart the characteristic horseshoe curvature to proteins with 20- to 30-residue repeats [PUBMED:11967365].
These are small, all beta strand domains, structurally described for the protein Internalin (InlA) and related proteins InlB, InlE, InlH from the pathogenic bacterium Listeria monocytogenes. Their function appears to be mainly structural: They are fused to the C-terminal end of leucine-rich repeats (LRR), 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 [PUBMED:11575932, PUBMED:12526809, PUBMED:15003459].
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan E-set (CL0159), which has the following description:
This clan includes a diverse range of domains that have an Ig-like fold and appear to be distantly related to each other. The clan includes: PKD domains, cadherins and several families of bacterial Ig-like domains as well as viral tail fibre proteins. it also includes several Fibronectin type III domain-containing families.
The clan contains the following 218 members:
A2M A2M_BRD A2M_recep Adeno_GP19K AlcCBM31 Alpha-amylase_N Alpha_adaptinC2 Alpha_E2_glycop Arch_flagellin Arylsulfotran_N ASF1_hist_chap ATG19_autophagy BACON Big_1 Big_10 Big_11 Big_2 Big_3 Big_3_2 Big_3_3 Big_3_5 Big_4 Big_5 Big_6 Big_7 Big_8 Big_9 Bile_Hydr_Trans BiPBP_C bMG1 bMG10 bMG3 bMG5 bMG6 BslA BsuPI Cadherin Cadherin-like Cadherin_2 Cadherin_3 Cadherin_4 Cadherin_5 Cadherin_pro CagX Calx-beta Candida_ALS_N CARDB CBM39 CBM_X2 CD45 CelD_N Ceramidse_alk_C CHB_HEX_C CHB_HEX_C_1 ChitinaseA_N ChiW_Ig_like CHU_C Coatamer_beta_C COP-gamma_platf CopC Cyc-maltodext_N Cytomega_US3 DsbC DUF11 DUF1410 DUF1425 DUF1929 DUF2271 DUF3244 DUF3327 DUF3416 DUF3458 DUF3501 DUF3823_C DUF3859 DUF3872 DUF4165 DUF4179 DUF4426 DUF4448 DUF4469 DUF4625 DUF4879 DUF4981 DUF4982 DUF5001 DUF5008 DUF5011 DUF5065 DUF5115 DUF525 DUF5643 DUF916 EB_dh ECD EpoR_lig-bind ERAP1_C EstA_Ig_like Filamin FixG_C Flavi_glycop_C FlgD_ig fn3 Fn3-like fn3_2 fn3_4 fn3_5 fn3_6 FN3_7 Fn3_assoc fn3_PAP GBS_Bsp-like Glucodextran_B Glyco_hydro2_C5 Glyco_hydro_2 Glyco_hydro_61 Gmad2 GMP_PDE_delta GPI-anchored Hanta_G1 He_PIG He_PIG_assoc HECW_N HemeBinding_Shp Hemocyanin_C Herpes_BLLF1 HYR IFNGR1 Ig_GlcNase Ig_mannosidase IL12p40_C Il13Ra_Ig IL17R_fnIII_D1 IL17R_fnIII_D2 IL2RB_N1 IL3Ra_N IL4Ra_N IL6Ra-bind Inhibitor_I42 Inhibitor_I71 Integrin_alpha2 Interfer-bind Invasin_D3 IRK_C IrmA Iron_transport LEA_2 Lep_receptor_Ig LIFR_N Lipase_bact_N LPMO_10 LRR_adjacent LTD Mannosidase_ig MG1 MG2 MG3 MG4 Mo-co_dimer N_BRCA1_IG Na_K-ATPase NEAT Neocarzinostat Neurexophilin NPCBM_assoc PapD_C PBP-Tp47_c Peptidase_C25_C Phlebovirus_G2 PhoD_N PKD PKD_2 PKD_3 Pollen_allerg_1 Pox_vIL-18BP Pur_ac_phosph_N Qn_am_d_aII Qn_am_d_aIII RabGGT_insert Reeler REJ RET_CLD1 RET_CLD3 RET_CLD4 RGI_lyase RHD_dimer Rho_GDI Rib SCAB-Ig SKICH SLAM SoxZ SprB SusE SVA SWM_repeat T2SS-T3SS_pil_N Tafi-CsgC TarS_C1 TcA_RBD TcfC TIG TIG_2 TIG_plexin Tissue_fac Top6b_C Transglut_C Transglut_N TRAP_beta Tuberculin UL16 Velvet WIF Wzt_C Y_Y_Y YBD ZirS_C Zona_pellucidaAlignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
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Full (129) |
Representative proteomes | UniProt (1594) |
NCBI (5544) |
Meta (3) |
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| RP15 (21) |
RP35 (43) |
RP55 (120) |
RP75 (260) |
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| PP/heatmap | 1 | ||||||||
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| Seed (10) |
Full (129) |
Representative proteomes | UniProt (1594) |
NCBI (5544) |
Meta (3) |
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|---|---|---|---|---|---|---|---|---|---|
| RP15 (21) |
RP35 (43) |
RP55 (120) |
RP75 (260) |
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| Raw Stockholm | |||||||||
| Gzipped | |||||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
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Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | Pfam-B_1177 (release 16.0) |
| Previous IDs: | none |
| Type: | Family |
| Sequence Ontology: | SO:0100021 |
| Author: |
Mistry J  , Schubert WD
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| Number in seed: | 10 |
| Number in full: | 129 |
| Average length of the domain: | 49.10 aa |
| Average identity of full alignment: | 34 % |
| Average coverage of the sequence by the domain: | 9.23 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 57 | ||||||||||||
| Family (HMM) version: | 11 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Colour assignments
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Interactions
Structures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the LRR_adjacent domain has been found. There are 39 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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