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. PMID 14747988. S2CID 19951452.
^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. S2CID 84294221.
^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.
^ 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. PMID 8946850. S2CID 36535731.
^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. S2CID 17232767.
^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 readingedit
Tooze, John; Brändén, Carl-Ivar (1999). Introduction to Protein Structure (2nd ed.). New York: Garland Publishing. ISBN0-8153-2305-0.
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. PMC2645405. PMID 18986514.
This article incorporates text from the public domain Pfam and InterPro: IPR012569
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This article incorporates text from the public domain Pfam and InterPro: IPR000372
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This article incorporates text from the public domain Pfam and InterPro: IPR004830
This article incorporates text from the public domain Pfam and InterPro: IPR004830
April 12, 2024
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A leucine rich repeat LRR is a protein structural motif that forms an a b 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 An example of a leucine rich repeat protein a porcine ribonuclease inhibitorIdentifiersSymbolLRR 1PfamPF00560Pfam clanCL0022InterProIPR001611SCOP22bnh SCOPe SUPFAMMembranome605Available protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryLeucine rich repeat varianta leucine rich repeat variant with a novel repetitive protein structural motifIdentifiersSymbolLRVPfamPF01816Pfam clanCL0020InterProIPR004830SCOP21lrv SCOPe SUPFAMMembranome737Available protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryLRR adjacentinternalin h crystal structure of fused n terminal domains IdentifiersSymbolLRR adjacentPfamPF08191InterProIPR012569Membranome341Available protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryLeucine rich repeat N terminal domaindimeric bovine tissue extracted decorin crystal form 2IdentifiersSymbolLRRNTPfamPF01462InterProIPR000372SMARTLRRNTSCOP21m10 SCOPe SUPFAMMembranome127Available protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryLeucine rich repeat N terminal domainthe crystal structure of pgip polygalacturonase inhibiting protein a leucine rich repeat protein involved in plant defenseIdentifiersSymbolLRRNT 2PfamPF08263InterProIPR013210SMARTLRRNTSCOP21m10 SCOPe SUPFAMAvailable protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryLeucine rich repeat C terminal domainthird lrr domain of drosophila slitIdentifiersSymbolLRRCTPfamPF01463InterProIPR000483SMARTLRRCTSCOP21m10 SCOPe SUPFAMAvailable protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryLRV protein FeS4 clustera leucine rich repeat variant with a novel repetitive protein structural motifIdentifiersSymbolLRV FeSPfamPF05484Pfam clanCL0020InterProIPR008665SCOP21lrv SCOPe SUPFAMAvailable protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryLeucine rich repeats are frequently involved in the formation of protein protein interactions 3 4 Contents 1 Examples 2 Associated domains 3 See also 4 References 4 1 Further reading 5 External linksExamples editLeucine 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 editLeucine rich repeats are often flanked by N terminal and C terminal cysteine rich domains but not always as is the case with C5orf36They 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 editLeucine zipperReferences edit 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 S2CID 19951452 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 S2CID 84294221 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 S2CID 36535731 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 S2CID 17232767 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 edit Tooze John Branden 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 editEukaryotic Linear Motif resource motif class LIG SCF Skp2 Cks1 1 SCOP LRR fold CATH Alpha beta horseshoe architecture LRRML a conformational database of leucine rich repeats This article incorporates text from the public domain Pfam and InterPro IPR012569 This article incorporates text from the public domain Pfam and InterPro IPR013210 This article incorporates text from the public domain Pfam and InterPro IPR000372 This article incorporates text from the public domain Pfam and InterPro IPR000483 This article incorporates text from the public domain Pfam and InterPro IPR004830 This article incorporates text from the public domain Pfam and InterPro IPR004830 Retrieved from https en wikipedia org w index php title Leucine rich repeat amp oldid 1187413281, wikipedia, wiki, book, books, library,
