In many cases the trefoil knot is part of the active site or a ligand-binding site and is critical to the activity of the enzyme in which it appears. Before the discovery of the first knotted protein, it was believed that the process of protein folding could not efficiently produce deep knots in protein backbones. Studies of the folding kinetics of a dimeric protein from Haemophilus influenzae have revealed that the folding of trefoil knot proteins may depend on proline isomerization.[5] Computational algorithms have been developed to identify knotted protein structures, both to canvas the Protein Data Bank for previously undetected natural knots and to identify knots in protein structure predictions, where they are unlikely to accurately reproduce the native-state structure due to the rarity of knots in known proteins.[6] Knottins are small, diverse and stable proteins with important drug design potential. They can be classified in 30 families which cover a wide range of sequences (1621 sequenced), three-dimensional structures (155 solved) and functions (> 10). Inter knottin similarity lies mainly between 20% and 40% sequence identity and 1.5 to 4 A backbone deviations although they all share a tightly knotted disulfide core. This important variability is likely to arise from the highly diverse loops which connect the successive knotted cysteines. The prediction of structural models for all knottin sequences would open new directions for the analysis of interaction sites and to provide a better understanding of the structural and functional organization of proteins sharing this scaffold.[7]
Trefoil (P-type) domain is a cysteine-rich domain of approximately forty five amino-acid residues has been found in some extracellular eukaryotic proteins.[9][10][11][12] It is known as either the 'P', 'trefoil' or 'TFF' domain, and contains six cysteines linked by three disulphide bonds with connectivity 1–5, 2–4, 3–6.
The domain has been found in a variety of extracellular eukaryotic proteins,[9][11][12] including protein pS2 (TFF1) a protein secreted by the stomach mucosa; spasmolytic polypeptide (SP) (TFF2), a protein of about 115 residues that inhibits gastrointestinal motility and gastric acidsecretion; intestinal trefoil factor (ITF) (TFF3); Xenopus laevis stomach proteins xP1 and xP4; xenopus integumentary mucins A.1 (preprospasmolysin) and C.1, proteins which may be involved in defense against microbial infections by protecting the epithelia from the external environment; xenopus skin protein xp2 (or APEG); Zona pellucida sperm-binding protein B (ZP-B); intestinal sucrase-isomaltase (EC 3.2.1.48 / EC 3.2.1.10), a vertebrate membrane bound, multifunctional enzyme complex which hydrolyzes sucrose, maltose and isomaltose; and lysosomal alpha-glucosidase (EC 3.2.1.20).
Examplesedit
Human gene encoding proteins containing the trefoil domain include:
There was a web server pKNOT available to detect knots in proteins as well as to provide information on knotted proteins in the Protein Data Bank.[13]
Referencesedit
^Zarembinski, Thomas I.; Kim, Youngchang; Peterson, Kelly; Christendat, Dinesh; Dharamsi, Akil; Arrowsmith, Cheryl H.; Edwards, Aled M.; Joachimiak, Andrzej (2002). "Deep trefoil knot implicated in RNA binding found in an archaebacterial protein". Proteins: Structure, Function, and Bioinformatics. 50 (2): 177–183. doi:10.1002/prot.10311. PMC2792022. PMID 12486711.
^Nureki, Osamu; Shirouzu, Mikako; Hashimoto, Kyoko; Ishitani, Ryuichiro; Terada, Takaho; Tamakoshi, Masatada; Oshima, Tairo; Chijimatsu, Masao; Takio, Koji; Vassylyev, Dmitry G.; Shibata, Takehiko; Inoue, Yorinao; Kuramitsu, Seiki; Yokoyama, Shigeyuki (2002). "An enzyme with a deep trefoil knot for the active-site architecture". Acta Crystallographica Section D Biological Crystallography. 58 (7): 1129–1137. doi:10.1107/s0907444902006601. PMID 12077432.
^Nureki, Osamu; Watanabe, Kazunori; Fukai, Shuya; Ishii, Ryohei; Endo, Yaeta; Hori, Hiroyuki; Yokoyama, Shigeyuki (2004). "Deep Knot Structure for Construction of Active Site and Cofactor Binding Site of tRNA Modification Enzyme". Structure. 12 (4): 593–602. doi:10.1016/j.str.2004.03.003. PMID 15062082.
^Leulliot, N.; Bohnsack, M. T.; Graille, M.; Tollervey, D.; Van Tilbeurgh, H. (2007). "The yeast ribosome synthesis factor Emg1 is a novel member of the superfamily of alpha/Beta knot fold methyltransferases". Nucleic Acids Research. 36 (2): 629–639. doi:10.1093/nar/gkm1074. PMC2241868. PMID 18063569.
^Mallam, Anna L.; Jackson, Sophie E. (2006). "Probing Nature's Knots: The Folding Pathway of a Knotted Homodimeric Protein". Journal of Molecular Biology. 359 (5): 1420–1436. doi:10.1016/j.jmb.2006.04.032. PMID 16787779.
^Khatib, Firas; Weirauch, Matthew T.; Rohl, Carol A. (2006). "Rapid knot detection and application to protein structure prediction". Bioinformatics. 22 (14): e252–e259. doi:10.1093/bioinformatics/btl236. PMID 16873480.
^Gracy, Jérôme; Chiche, Laurent (2010). "Optimizing structural modeling for a specific protein scaffold: Knottins or inhibitor cystine knots". BMC Bioinformatics. 11: 535. doi:10.1186/1471-2105-11-535. PMC2984590. PMID 21029427.
^Gajhede M, Petersen TN, Henriksen A, et al. (December 1993). "Pancreatic spasmolytic polypeptide: first three-dimensional structure of a member of the mammalian trefoil family of peptides". Structure. 1 (4): 253–62. doi:10.1016/0969-2126(93)90014-8. PMID 8081739.
^ abOtto B, Wright N (1994). "Trefoil peptides. Coming up clover". Current Biology. 4 (9): 835–838. doi:10.1016/S0960-9822(00)00186-X. PMID 7820556. S2CID 11245174.
^Thim L, Wright NA, Hoffmann W, Otto WR, Rio MC (1997). "Rolling in the clover: trefoil factor family (TFF)-domain peptides, cell migration and cancer". FEBS Letters. 408 (2): 121–123. doi:10.1016/S0014-5793(97)00424-9. PMID 9187350. S2CID 26946754.
^ abBork P (1993). "A trefoil domain in the major rabbit zona pellucida protein". Protein Science. 2 (4): 669–670. doi:10.1002/pro.5560020417. PMC2142363. PMID 8518738.
^ abHoffmann W, Hauser F (1993). "The P-domain or trefoil motif: a role in renewal and pathology of mucous epithelia?". Trends in Biochemical Sciences. 18 (7): 239–243. doi:10.1016/0968-0004(93)90170-R. PMID 8267796.
^Lai, Y.-L.; Yen, S.-C.; Yu, S.-H.; Hwang, J.-K. (2007). "pKNOT: The protein KNOT web server". Nucleic Acids Research. 35 (Web Server issue): W420–W424. doi:10.1093/nar/gkm304. PMC1933195. PMID 17526524.
External linksedit
SCOP alpha/beta knot fold
Bibliographyedit
Tkaczuk KL, Dunin-Horkawicz S, Purta E, Bujnicki JM. (2007). Structural and evolutionary bioinformatics of the SPOUT superfamily of methyltransferases. BMC Bioinformatics. 8:73
This article incorporates text from the public domain Pfam and InterPro: IPR000519
January 01, 1970
trefoil, knot, fold, trefoil, knot, fold, protein, fold, which, protein, backbone, twisted, into, trefoil, knot, shape, shallow, knots, which, tail, polypeptide, chain, only, passes, through, loop, residues, uncommon, deep, knots, which, many, residues, passed. The trefoil knot fold is a protein fold in which the protein backbone is twisted into a trefoil knot shape Shallow knots in which the tail of the polypeptide chain only passes through a loop by a few residues are uncommon but deep knots in which many residues are passed through the loop are extremely rare Deep trefoil knots have been found in the SPOUT superfamily 1 including methyltransferase proteins involved in posttranscriptional RNA modification in all three domains of life including bacterium Thermus thermophilus 2 and proteins 3 in archaea 1 and in eukaryota 4 A deep trefoil knot in a Thermus thermophilus RNA methyltransferase domain PDB ID 1IPA The knotted C terminus of the protein is shown in blue In many cases the trefoil knot is part of the active site or a ligand binding site and is critical to the activity of the enzyme in which it appears Before the discovery of the first knotted protein it was believed that the process of protein folding could not efficiently produce deep knots in protein backbones Studies of the folding kinetics of a dimeric protein from Haemophilus influenzae have revealed that the folding of trefoil knot proteins may depend on proline isomerization 5 Computational algorithms have been developed to identify knotted protein structures both to canvas the Protein Data Bank for previously undetected natural knots and to identify knots in protein structure predictions where they are unlikely to accurately reproduce the native state structure due to the rarity of knots in known proteins 6 Knottins are small diverse and stable proteins with important drug design potential They can be classified in 30 families which cover a wide range of sequences 1621 sequenced three dimensional structures 155 solved and functions gt 10 Inter knottin similarity lies mainly between 20 and 40 sequence identity and 1 5 to 4 A backbone deviations although they all share a tightly knotted disulfide core This important variability is likely to arise from the highly diverse loops which connect the successive knotted cysteines The prediction of structural models for all knottin sequences would open new directions for the analysis of interaction sites and to provide a better understanding of the structural and functional organization of proteins sharing this scaffold 7 Contents 1 Trefoil domain 1 1 Examples 2 History 3 References 4 External links 5 BibliographyTrefoil domain editTrefoil P type domain nbsp Structure of pancreatic spasmolytic polypeptide 8 IdentifiersSymbolTrefoilPfamPF00088InterProIPR000519SMARTSM00018PROSITEPDOC00024SCOP21psp SCOPe SUPFAMCDDcd00111Available protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryPDB1e9t A 31 72 1pe3 2 31 72 1ps2 30 71 1hi7 B 30 71 2psp A 28 70 1psp B 28 70 1pcp 28 70 Trefoil P type domain is a cysteine rich domain of approximately forty five amino acid residues has been found in some extracellular eukaryotic proteins 9 10 11 12 It is known as either the P trefoil or TFF domain and contains six cysteines linked by three disulphide bonds with connectivity 1 5 2 4 3 6 The domain has been found in a variety of extracellular eukaryotic proteins 9 11 12 including protein pS2 TFF1 a protein secreted by the stomach mucosa spasmolytic polypeptide SP TFF2 a protein of about 115 residues that inhibits gastrointestinal motility and gastric acid secretion intestinal trefoil factor ITF TFF3 Xenopus laevis stomach proteins xP1 and xP4 xenopus integumentary mucins A 1 preprospasmolysin and C 1 proteins which may be involved in defense against microbial infections by protecting the epithelia from the external environment xenopus skin protein xp2 or APEG Zona pellucida sperm binding protein B ZP B intestinal sucrase isomaltase EC 3 2 1 48 EC 3 2 1 10 a vertebrate membrane bound multifunctional enzyme complex which hydrolyzes sucrose maltose and isomaltose and lysosomal alpha glucosidase EC 3 2 1 20 Examples edit Human gene encoding proteins containing the trefoil domain include acid alpha glucosidase MGAM TFF1 TFF2 TFF3 and ZP4 History editThere was a web server pKNOT available to detect knots in proteins as well as to provide information on knotted proteins in the Protein Data Bank 13 References edit Zarembinski Thomas I Kim Youngchang Peterson Kelly Christendat Dinesh Dharamsi Akil Arrowsmith Cheryl H Edwards Aled M Joachimiak Andrzej 2002 Deep trefoil knot implicated in RNA binding found in an archaebacterial protein Proteins Structure Function and Bioinformatics 50 2 177 183 doi 10 1002 prot 10311 PMC 2792022 PMID 12486711 Nureki Osamu Shirouzu Mikako Hashimoto Kyoko Ishitani Ryuichiro Terada Takaho Tamakoshi Masatada Oshima Tairo Chijimatsu Masao Takio Koji Vassylyev Dmitry G Shibata Takehiko Inoue Yorinao Kuramitsu Seiki Yokoyama Shigeyuki 2002 An enzyme with a deep trefoil knot for the active site architecture Acta Crystallographica Section D Biological Crystallography 58 7 1129 1137 doi 10 1107 s0907444902006601 PMID 12077432 Nureki Osamu Watanabe Kazunori Fukai Shuya Ishii Ryohei Endo Yaeta Hori Hiroyuki Yokoyama Shigeyuki 2004 Deep Knot Structure for Construction of Active Site and Cofactor Binding Site of tRNA Modification Enzyme Structure 12 4 593 602 doi 10 1016 j str 2004 03 003 PMID 15062082 Leulliot N Bohnsack M T Graille M Tollervey D Van Tilbeurgh H 2007 The yeast ribosome synthesis factor Emg1 is a novel member of the superfamily of alpha Beta knot fold methyltransferases Nucleic Acids Research 36 2 629 639 doi 10 1093 nar gkm1074 PMC 2241868 PMID 18063569 Mallam Anna L Jackson Sophie E 2006 Probing Nature s Knots The Folding Pathway of a Knotted Homodimeric Protein Journal of Molecular Biology 359 5 1420 1436 doi 10 1016 j jmb 2006 04 032 PMID 16787779 Khatib Firas Weirauch Matthew T Rohl Carol A 2006 Rapid knot detection and application to protein structure prediction Bioinformatics 22 14 e252 e259 doi 10 1093 bioinformatics btl236 PMID 16873480 Gracy Jerome Chiche Laurent 2010 Optimizing structural modeling for a specific protein scaffold Knottins or inhibitor cystine knots BMC Bioinformatics 11 535 doi 10 1186 1471 2105 11 535 PMC 2984590 PMID 21029427 Gajhede M Petersen TN Henriksen A et al December 1993 Pancreatic spasmolytic polypeptide first three dimensional structure of a member of the mammalian trefoil family of peptides Structure 1 4 253 62 doi 10 1016 0969 2126 93 90014 8 PMID 8081739 a b Otto B Wright N 1994 Trefoil peptides Coming up clover Current Biology 4 9 835 838 doi 10 1016 S0960 9822 00 00186 X PMID 7820556 S2CID 11245174 Thim L Wright NA Hoffmann W Otto WR Rio MC 1997 Rolling in the clover trefoil factor family TFF domain peptides cell migration and cancer FEBS Letters 408 2 121 123 doi 10 1016 S0014 5793 97 00424 9 PMID 9187350 S2CID 26946754 a b Bork P 1993 A trefoil domain in the major rabbit zona pellucida protein Protein Science 2 4 669 670 doi 10 1002 pro 5560020417 PMC 2142363 PMID 8518738 a b Hoffmann W Hauser F 1993 The P domain or trefoil motif a role in renewal and pathology of mucous epithelia Trends in Biochemical Sciences 18 7 239 243 doi 10 1016 0968 0004 93 90170 R PMID 8267796 Lai Y L Yen S C Yu S H Hwang J K 2007 pKNOT The protein KNOT web server Nucleic Acids Research 35 Web Server issue W420 W424 doi 10 1093 nar gkm304 PMC 1933195 PMID 17526524 External links editSCOP alpha beta knot fold CATH alpha beta knot topologyBibliography editTkaczuk KL Dunin Horkawicz S Purta E Bujnicki JM 2007 Structural and evolutionary bioinformatics of the SPOUT superfamily of methyltransferases BMC Bioinformatics 8 73 This article incorporates text from the public domain Pfam and InterPro IPR000519 Retrieved from https en wikipedia org w index php title Trefoil knot fold amp oldid 1184192799 Trefoil domain, wikipedia, wiki, book, books, library,
