- Publisher
- Elsevier
- Copyright
- Copyright © 2002 Elsevier Ltd
- ISSN
- 0022-2836
- DOI
- 10.1016/S0022-2836(02)00736-2
- Publisher site
- See Article on Publisher Site
Abstract
Over the last decade, structural biologists have unravelled many proteins that appear natively disordered. Common assumptions are that many of these proteins adopt structure through binding and that the structural flexibility enables them to adopt different functions. Here, we investigated regions of more than 70 sequence-consecutive residues that have no regular secondary structure (NORS). Analysing 31 entirely sequenced organisms, we predicted five times as many proteins with NORS regions (loopy proteins) in eukaryotes (20%) than in prokaryotes and archaeas (4%). Thousands of these NORS regions were over 150 residues long. The amino acid composition of NORS regions differed from that of loops in PDB. Although NORS proteins had significantly more residues in low-complexity regions than other proteins, simple cut-off thresholds for sequence bias missed most NORS regions. On average, NORS regions were evolutionarily at least as conserved as their flanking regions. Furthermore, yeast proteins with NORS regions had more protein–protein interaction partners than other proteins. Regulatory and transcription-related functions were over-represented in loopy proteins, biosynthesis and energy metabolism were under-represented. Overall, our analysis confirmed that proteins with non-regular structures appear to play important functional roles, and they may adopt as yet unknown types of protein structures.
Journal
Journal of Molecular Biology – Elsevier
Published: Sep 6, 2002
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References
-
Experimental and theoretical aspects of protein foldingAnfinsen, C.B.; Scheraga, H.A.
-
Sequence does specify protein conformationEllis, R.J.; Dobson, C.; Hartl, U.
-
Principles that govern the folding of protein chainsAnfinsen, C.B.
-
Functional diversity of PH domains: an exhaustive modelling studyBlomberg, N.; Nilges, M.
-
Protein–DNA interactions: a structural analysisJones, S.; van Heyningen, P.; Berman, H.M.; Thornton, J.M.
-
Structure-based analysis of catalysis and substrate definition in the HIT protein familyLima, C.D.; Klein, M.G.; Hendrickson, W.A.
-
From fold to functionMoult, J.; Melamud, E.
-
Structural classification of proteins: new superfamiliesMurzin, A.G.
-
Evolution of function in protein superfamilies, from a structural perspectiveTodd, A.E.; Orengo, C.A.; Thornton, J.M.
-
Protein–RNA interactions: a structural analysisJones, S.; Daley, D.T.; Luscombe, N.M.; Berman, H.M.; Thornton, J.M.
-
Protein structural alignments and functional genomicsIrving, J.A.; Whisstock, J.C.; Lesk, A.M.
-
Detection of protein three-dimensional side-chain patterns: new examples of convergent evolutionRussell, R.B.
-
TESS: a geometric hashing algorithm for deriving 3D coordinate templates for searching structural databases. Application to enzyme active sitesWallace, A.C.; Borkakoti, N.; Thornton, J.M.
-
Endocytosis and signals for internalizationTrowbridge, I.S.
-
The nicotinic acetylcholine receptor of the Torpedo electric rayUnwin, N.
-
Predicting conformational switches in proteinsYoung, M.; Kirshenbaum, K.; Dill, K.A.; Highsmith, S.
-
The time scale of the catalytic loop motion in triosephosphate isomeraseRozovsky, S.; McDermott, A.E.
-
Solution-state NMR investigations of triosephosphate isomerase active site loop motion: ligand release in relation to active site loop dynamicsRozovsky, S.; Jogl, G.; Tong, L.; McDermott, A.E.
-
Intrinsically unstructured proteins: re-assessing the protein structure–function paradigmWright, P.E.; Dyson, H.J.
-
What are enzyme structures telling us?Perutz, M.F.
-
Structures of Escherichia coli branched-chain amino acid aminotransferase and its complexes with 4-methylvalerate and 2-methylleucine: induced fit and substrate recognition of the enzymeOkada, K.; Hirotsu, K.; Hayashi, H.; Kagamiyama, H.
-
A succession of substrate induced conformational changes ensures the amino acid specificity of Thermus thermophilus prolyl-tRNA synthetase: comparison with histidyl-tRNA synthetaseYaremchuk, A.; Tukalo, M.; Grotli, M.; Cusack, S.
-
FlexE: efficient molecular docking considering protein structure variationsClaussen, H.; Buning, C.; Rarey, M.; Lengauer, T.
-
Floppy SOX: mutual induced fit in hmg (high-mobility group) box-DNA recognitionWeiss, M.A.
-
The antigenic structure of the HIV gp120 envelope glycoproteinWyatt, R.; Kwong, P.D.; Desjardins, E.; Sweet, R.W.; Robinson, J.; Hendrickson, W.A.; Sodroski, J.G.
-
pH-dependent and ligand induced conformational changes of eucaryotic protein synthesis initiation factor eIF-(iso)4F: a circular dichroism studyWang, Y.; Sha, M.; Ren, W.Y.; van Heerden, A.; Browning, K.S.; Goss, D.J.
-
Induced fit in arginine kinaseZhou, G.; Ellington, W.R.; Chapman, M.S.
-
Intrinsically disordered proteinDunker, A.K.; Lawson, J.D.; Brown, C.J.; Williams, R.M.; Romero, P.; Oh, J.S.
-
Calcineurin: a member of a family of calmodulin-stimulated protein phosphatasesManalan, A.S.; Krinks, M.H.; Klee, C.B.
-
Activation of calcineurin by limited proteolysisManalan, A.S.; Klee, C.B.
-
Crystal structures of human calcineurin and the human FKBP12–FK506–calcineurin complexKissinger, C.R.; Parge, H.E.; Knighton, D.R.; Lewis, C.T.; Pelletier, L.A.; Tempczyk, A.
-
Roles of partly unfolded conformations in macromolecular self-assemblyNamba, K.
-
Protein disorder and the evolution of molecular recognition: theory, predictions and observationsDunker, A.K.; Garner, E.; Guilliot, S.; Romero, P.; Albrecht, K.; Hart, J.
-
Predicting disordered regions from amino acid sequence: common themes despite differing structural characterization. Genome inform ser workshopGarner, E.; Cannon, P.; Romero, P.; Obradovic, Z.; Dunker, A.K.
-
Analysis of compositionally biased regions in sequence databasesWootton, J.C.; Federhen, S.
-
The protein trinity-linking function and disorderDunker, A.K.; Obradovic, Z.
-
Thousands of proteins likely to have long disordered regionsRomero, P.; Obradovic, Z.; Kissinger, C.R.; Villafranca, J.E.; Garner, E.; Guilliot, S.; Dunker, A.K.
-
Sequence complexity of disordered proteinRomero, P.; Obradovic, Z.; Li, X.; Garner, E.C.; Brown, C.J.; Dunker, A.K.
-
The SWISS-PROT:protein sequence database and its supplement TrEMBL in 2000Bairoch, A.; Apweiler, R.
-
The Protein Data BankBerman, H.M.; Westbrook, J.; Feng, Z.; Gillliland, G.; Bhat, T.N.; Weissig, H.
-
Crystal structure of formate dehydrogenase H: catalysis involving Mo, molybdopterin, selenocysteine, and an Fe4S4 clusterBoyington, J.C.; Gladyshev, V.N.; Khangulov, S.V.; Stadtman, T.C.; Sun, P.D.
-
Three-dimensional structure of Pseudomonas isoamylase at 2.2 Å resolutionKatsuya, Y.; Mezaki, Y.; Kubota, M.; Matsuura, Y.
-
Canine parvovirus capsid structure, analyzed at 2.9 Å resolutionXie, Q.; Chapman, M.S.
-
The refined crystal structure of hexon, the major coat protein of adenovirus type 2, at 2.9 Canine parvovirus capsid structure, analyzed at 2.9 Å resolution resolutionAthappilly, F.K.; Murali, R.; Rux, J.J.; Cai, Z.; Burnett, R.M.
-
The crystal structure of cricket paralysis virus: the first view of a new virus familyTate, J.; Liljas, L.; Scotti, P.; Christian, P.; Lin, T.; Johnson, J.E.
-
Crystal structures of the key anaerobic enzyme pyruvate:ferredoxin oxidoreductase, free and in complex with pyruvateChabriere, E.; Charon, M.H.; Volbeda, A.; Pieulle, L.; Hatchikian, E.C.; Fontecilla-Camps, J.C.
-
The refined crystal structure of an endochitinase from Hordeum vulgare L. seeds at 1.8 Å resolutionHart, P.J.; Pfluger, H.D.; Monzingo, A.F.; Hollis, T.; Robertus, J.D.
-
The active center of catalaseFita, I.; Rossmann, M.G.
-
The NADPH binding site on beef liver catalaseFita, I.; Rossmann, M.G.
-
The crystal structure of chloroperoxidase: a heme peroxidase–cytochrome P450 functional hybridSundaramoorthy, M.; Terner, J.; Poulos, T.L.
-
Extracellular domain of type I receptor for transforming growth factor-beta: molecular modelling using protectin (CD59) as a templateJokiranta, T.S.; Tissari, J.; Teleman, O.; Meri, S.
-
Structural studies of HIV-1 Tat proteinBayer, P.; Kraft, M.; Ejchart, A.; Westendorp, M.; Frank, R.; Rosch, P.
-
The solution structure of type II antifreeze protein reveals a new member of the lectin familyGronwald, W.; Loewen, M.C.; Lix, B.; Daugulis, A.J.; Sonnichsen, F.D.; Davies, P.L.; Sykes, B.D.
-
Crystal structure of the complex of carboxypeptidase A with a strongly bound phosphonate in a new crystalline form: comparison with structures of other complexesKim, H.; Lipscomb, W.N.
-
Dictionary of protein secondary structure: pattern recognition of hydrogen bonded and geometrical featuresKabsch, W.; Sander, C.
-
Accuracy of protein flexibility predictionsVihinen, M.; Torkkila, E.; Riikonen, P.
-
Multiple sequence threading: an analysis of alignment quality and stabilityTaylor, W.R.
-
Applying motif and profile searchesBork, P.; Gibson, T.J.
-
The COG database: new developments in phylogenetic classification of proteins from complete genomesTatusov, R.L.; Natale, D.A.; Garkavtsev, I.V.; Tatusova, T.A.; Shankavaram, U.T.; Rao, B.S.
-
Analysis of insertions/deletions in protein structuresPascarella, S.; Argos, P.
-
DIP, the Database of Interacting Proteins: a research tool for studying cellular networks of protein interactionsXenarios, I.; Salwinski, L.; Duan, X.J.; Higney, P.; Kim, S.M.; Eisenberg, D.
-
A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiaeUetz, P.; Giot, L.; Cagney, G.; Mansfield, T.A.; Judson, R.S.; Knight, J.R.
-
The protein–protein interaction map of Helicobacter pyloriRain, J.C.; Selig, L.; De Reuse, H.; Battaglia, V.; Reverdy, C.; Simon, S.
-
A protein–protein interaction map of yeast RNA polymerase IIIFlores, A.; Briand, J.F.; Gadal, O.; Andrau, J.C.; Rubbi, L.; Van Mullem, V.
-
Genome-wide protein interaction screens reveal functional networks involving Sm-like proteinsFromont-Racine, M.; Mayes, A.E.; Brunet-Simon, A.; Rain, J.C.; Colley, A.; Dix, I.
-
A network of proteins around Rvs167p and Rvs161p, two proteins related to the yeast actin cytoskeletonBon, E.; Recordon-Navarro, P.; Durrens, P.; Iwase, M.; Toh, E.A.; Aigle, M.
-
Function of the gene products in Escherichia coliRiley, M.
-
Protein evolution viewed through Escherichia coli protein sequences: introducing the notion of a structural segment of homology, the moduleRiley, M.; Labedan, B.
-
Genomes with distinct function compositionTamames, J.; Ouzounis, C.; Sander, C.; Valencia, A.
-
EUCLID: automatic classification of proteins in functional classes by their database annotationsTamames, J.; Ouzounis, C.; Casari, G.; Sander, C.; Valencia, A.
-
Practical limits of function predictionDevos, D.; Valencia, A.
-
Continuous assignment of secondary structure correlates with protein flexibilityAndersen, C.A.F.; Palmer, A.G.; Brunak, S.; Rost, B.
-
Why are “natively unfolded” proteins unstructured under physiologic conditions?Uversky, V.N.; Gillespie, J.R.; Fink, A.L.
-
A molecular switch for biochemical logic gates: conformational studiesAshkenazi, G.; Ripoll, D.R.; Lotan, N.; Scheraga, H.A.
-
Model of the ran–RCC1 interaction using biochemical and docking experimentsAzuma, Y.; Renault, L.; Garcia-Ranea, J.A.; Valencia, A.; Nishimoto, T.; Wittinghofer, A.
-
Structural changes in GroEL effected by binding a denatured protein substrateFalke, S.; Fisher, M.T.; Gogol, E.P.
-
Turning off the Ras switch with the flick of a fingerNoel, J.R.
-
Mechanisms by which IkappaB proteins control NF-kappaB activitySimeonidis, S.; Stauber, D.; Chen, G.; Hendrickson, W.A.; Thanos, D.
-
Towards understanding a molecular switch mechanism: thermodynamic and crystallographic studies of the signal transduction protein cheYSola, M.; Lopez-Hernandez, E.; Cronet, P.; Lacroix, E.; Serrano, L.; Coll, M.; Parraga, A.
-
A single residue substitution causes a switch from the dual DNA binding specificity of plant transcription factor MYB.Ph3 to the animal c-MYB specificitySolano, R.; Fuertes, A.; Sanchez-Pulido, L.; Valencia, A.; Paz-Ares, J.
-
How does the switch II region of G-domains work?Stouten, P.F.W.; Sander, C.; Wittinghofer, A.; Valencia, A.
-
Predicting allosteric switches in myosinsKirshenbaum, K.; Young, M.; Highsmith, S.
-
A conserved helix-unfolding motif in the naturally unfolded proteinsZetina, C.R.
-
Crystal structures of human calcineurin and the human FKBP12–FK506–calcineurin complexKissinger, C.R.; Parge, H.E.; Knighton, D.R.; Lewis, C.T.; Pelletier, L.A.; Tempczyk, A.
-
Target enzyme recognition by calmodulin: 2.4 Å structure of a calmodulin–peptide complexMeador, W.E.; Means, A.R.; Quiocho, F.A.
-
Finding function through structural genomicsShapiro, L.; Harris, T.
-
Structural genomics: beyond the human genome projectBurley, S.K.; Almo, S.C.; Bonanno, J.B.; Capel, M.; Chance, M.R.; Gaasterland, T.
-
100,000 protein structures for the biologistSali, A.
-
Marrying structure and genomicsRost, B.
-
Structural genomics: an overviewBlundell, T.L.; Mizuguchi, K.
-
Structural genomics taking shapeGaasterland, T.
-
Structural genomics takes offThornton, J.
-
Twilight zone of protein sequence alignmentsRost, B.
-
EVA: continuous automatic evaluation of protein structure prediction serversEyrich, V.; MartÍ-Renom, M.A.; Przybylski, D.; Fiser, A.; Pazos, F.; Valencia, A.
-
Database of homology-derived structures and the structural meaning of sequence alignmentSander, C.; Schneider, R.
-
Combining evolutionary information and neural networks to predict protein secondary structureRost, B.; Sander, C.
-
Prediction of protein secondary structure at better than 70% accuracyRost, B.; Sander, C.
-
Conservation and prediction of solvent accessibility in protein familiesRost, B.; Sander, C.
-
Topology prediction for helical transmembrane proteins at 86% accuracyRost, B.; Casadio, R.; Fariselli, P.
-
Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sitesNielsen, H.; Engelbrecht, J.; Brunak, S.; von Heijne, G.
-
Prediction and analysis of coiled-coil structuresLupas, A.
-
The minimal gene complement of Mycoplasma genitaliumFraser, C.M.; Gocayne, J.D.; White, O.; Adams, M.D.; Clayton, R.A.; Fleischmann, R.D.; Kelley, J.M.
-
Displaying the information contents of structural RNA alignments: the structure logosGorodkin, J.; Heyer, L.J.; Brunak, S.; Stormo, G.D.
-
Structure of the RGD protein decorsin: conserved motif and distinct function in leech proteins that affect blood clottingKrezel, A.M.; Wagner, G.; Seymour-Ulmer, J.; Lazarus, R.A.
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