Natively Disordered Proteins

Romero, Pedro; Obradović, Zoran; Dunker, A. Keith

doi:10.1002/9783527619498.ch41

Cited by 156 publications

(203 citation statements)

References 410 publications

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“…20,[25][26][27][28][29] These methods include NMR spectroscopy; 20,26,[30][31][32] missing electron density in X-ray crystallography maps; 33 optical rotatory dispersion spectroscopy (ORD); 18,34 circular dichroism spectroscopy in the near-UV 35 and far-UV regions; 18,34,36,37 Raman spectroscopy and Raman optical activity; 38 Fourier transform infrared spectroscopy (FTIR); 18 gelfiltration, viscometry, small angle neutron scattering (SANS), small angle X-ray scattering (SAXS), sedimentation, and dynamic and static light scattering; 27,39,40 fluorescent spectroscopy; 27,40 aberrant mobility in SDS-gel electrophoresis; 41,42 limited proteolysis (including conventional limited proteolysis [43][44][45][46][47] pulse proteolysis, 48 limited proteolysis combined to combined mass spectrometry, 49 and rapid and simple thermal proteolysis FASTpp assays; 50 H/D exchange; 27 abnormal conformational stability;. 40,[51][52][53][54] immunochemical methods; 55,…”

Section: Introductionmentioning

confidence: 99%

“…In fact, it is now recognized that IDPs/IDPRs may contain collapsed disorder (where the intrinsic disorder is present in a molten globular form) and extended disorder (where intrinsic disorder is present in a form of random coil or pre-molten globule) under physiological conditions in vitro. 5,20,22 It has also been shown that, in addition to completely ordered and disordered regions, proteins may contain regions of semi-disorder; i.e., fragments that have »50% predicted probability to be ordered or disordered. 23 Such semi-disordered regions have been shown to play key roles in protein aggregation, and to participate in protein-protein interactions involving induced folding.…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, IDPs/ IDPRs, despite being biologically active, fail to form specific 3D structures and exist as highly dynamic structural ensembles, either at the secondary or at the tertiary level. 5,6,[16][17][18][19][20][21] Furthermore, intrinsic disorder is characterized by high structural heterogeneity. In fact, it is now recognized that IDPs/IDPRs may contain collapsed disorder (where the intrinsic disorder is present in a molten globular form) and extended disorder (where intrinsic disorder is present in a form of random coil or pre-molten globule) under physiological conditions in vitro.…”

Section: Introductionmentioning

confidence: 99%

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How disordered is my protein and what is its disorder for? A guide through the “dark side” of the protein universe

Lieutaud

Ferrón

Uversky

et al. 2016

Intrinsically Disordered Proteins

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In the last 2 decades it has become increasingly evident that a large number of proteins are either fully or partially disordered. Intrinsically disordered proteins lack a stable 3D structure, are ubiquitous and fulfill essential biological functions. Their conformational heterogeneity is encoded in their amino acid sequences, thereby allowing intrinsically disordered proteins or regions to be recognized based on properties of these sequences. The identification of disordered regions facilitates the functional annotation of proteins and is instrumental for delineating boundaries of protein domains amenable to structural determination with X-ray crystallization. This article discusses a comprehensive selection of databases and methods currently employed to disseminate experimental and putative annotations of disorder, predict disorder and identify regions involved in induced folding. It also provides a set of detailed instructions that should be followed to perform computational analysis of disorder.KEYWORDS disorder databases and metaservers; induced folding; intrinsic disorder; intrinsically disordered proteins; intrinsically disordered regions; prediction methods

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

How disordered is my protein and what is its disorder for? A guide through the “dark side” of the protein universe

Lieutaud

Ferrón

Uversky

et al. 2016

Intrinsically Disordered Proteins

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“…Regions of some proteins had missing electron density, even in regions that were known to have function. 9 Thus, although the function of a protein is generally thought to arise from its unique and rigid 3-D structure, in some cases, the lack of structure (also known as intrinsic disorder) might be crucial for the function of many proteins, 10-23 especially proteins involved in signaling, recognition and regulation. [22][23][24][25] Recent studies revealed that intrinsic disorder is an abundant phenomenon and many proteins lack rigid 3-D structure under physiological conditions in vitro, existing instead as dynamic ensembles of interconverting structures.…”

Section: Introductionmentioning

confidence: 99%

Conservation of Intrinsic Disorder in Protein Domains and Families: I. A Database of Conserved Predicted Disordered Regions

et al. 2006

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Many protein regions have been shown to be intrinsically disordered, lacking unique structure under physiological conditions. These intrinsically disordered regions are not only very common in proteomes, they are also crucial to the function of many proteins, especially those involved in signaling, recognition, and regulation. The goal of this work was to identify the prevalence, characteristics, and functions of conserved disordered regions within protein domains and families.A database was created to store the amino acid sequences of nearly one million proteins and their domain matches from the InterPro database, a resource integrating eight different protein family and domain databases. Disorder prediction was performed on these protein sequences. Regions of sequence corresponding to domains were aligned using a multiple sequence alignment tool. From this initial information, regions of conserved predicted disorder were found within the domains. The methodology for this search consisted of finding regions of consecutive positions in the multiple sequence alignments in which a 90% or more of the sequences were predicted to be disordered. This procedure was constrained to find such regions of conserved disorder prediction that were at least 20 amino acids in length.The results of this work were 3,653 regions of conserved disorder prediction, found within 2,898 distinct InterPro entries. Most regions of conserved predicted disorder detected were short, with less than 10% of those found exceeding 30 residues in length.

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“…1, 2, 5, [8][9][10][11][12][13][14][15][16][17][18] Intrinsically disordered regions play a number of crucial roles in regulation, signaling and controlling processes where interactions with multiple partners and high-specificity/lowaffinity binding are involved. Many posttranslational modifications (including acetylation, hydroxylation, ubiquitination, methylation, phosphorylation, etc.)…”

Section: Introductionmentioning

confidence: 99%

Functional Anthology of Intrinsic Disorder. 2. Cellular Components, Domains, Technical Terms, Developmental Processes, and Coding Sequence Diversities Correlated with Long Disordered Regions

et al. 2007

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Biologically active proteins without stable ordered structure (i.e., intrinsically disordered proteins) are attracting increased attention. Functional repertoires of ordered and disordered proteins are very different, and the ability to differentiate whether a given function is associated with intrinsic disorder or with a well-folded protein is crucial for modern protein science. However, there is a large gap between the number of proteins experimentally confirmed to be disordered and their actual number in nature. As a result, studies of functional properties of confirmed disordered proteins, while helpful in revealing the functional diversity of protein disorder, provide only a limited view. To overcome this problem, a bioinformatics approach for comprehensive study of functional roles of protein disorder was proposed in the first paper of this series (Xie H., Vucetic S., Iakoucheva L.M., Oldfield C.J., Dunker A.K., Obradovic Z., Uversky V.N. (2006) Functional anthology of intrinsic disorder. I. Biological processes and functions of proteins with long disordered regions. J. Proteome Res.). Applying this novel approach to Swiss-Prot sequences and functional keywords, we found over 238 and 302 keywords to be strongly positively or negatively correlated, respectively, with long intrinsically disordered regions. This paper describes ~90 Swiss-Prot keywords attributed to the cellular components, domains, technical terms, developmental processes and coding sequence diversities possessing strong positive and negative correlation with long disordered regions.

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Natively Disordered Proteins

Cited by 156 publications

References 410 publications

How disordered is my protein and what is its disorder for? A guide through the “dark side” of the protein universe

How disordered is my protein and what is its disorder for? A guide through the “dark side” of the protein universe

Conservation of Intrinsic Disorder in Protein Domains and Families: I. A Database of Conserved Predicted Disordered Regions

Functional Anthology of Intrinsic Disorder. 2. Cellular Components, Domains, Technical Terms, Developmental Processes, and Coding Sequence Diversities Correlated with Long Disordered Regions

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