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

2006 ◽  
Vol 5 (4) ◽  
pp. 879-887 ◽  
Author(s):  
Jessica Walton Chen ◽  
Pedro Romero ◽  
Vladimir N. Uversky ◽  
A. Keith Dunker
Keyword(s):  
Protein Domains ◽  
Intrinsic Disorder ◽  
Disordered Regions

scholarly journals The Distinct Properties of the Consecutive Disordered Regions Inside or Outside Protein Domains and Their Functional Significance

2021 ◽  
Vol 22 (19) ◽  
pp. 10677
Author(s):  
Huqiang Wang ◽  
Haolin Zhong ◽  
Chao Gao ◽  
Jiayin Zang ◽  
Dong Yang
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Protein Domains ◽  
Comprehensive Analysis ◽  
Disordered Proteins ◽  
Functional Constraints ◽  
Biological Functions ◽  
Post Translational Modification ◽  
Intrinsically Disordered ◽  
And Function ◽  
Disordered Regions

The consecutive disordered regions (CDRs) are the basis for the formation of intrinsically disordered proteins, which contribute to various biological functions and increasing organism complexity. Previous studies have revealed that CDRs may be present inside or outside protein domains, but a comprehensive analysis of the property differences between these two types of CDRs and the proteins containing them is lacking. In this study, we investigated this issue from three viewpoints. Firstly, we found that in-domain CDRs are more hydrophilic and stable but have less stickiness and fewer post-translational modification sites compared with out-domain CDRs. Secondly, at the protein level, we found that proteins with only in-domain CDRs originated late, evolved rapidly, and had weak functional constraints, compared with the other two types of CDR-containing proteins. Proteins with only in-domain CDRs tend to be expressed spatiotemporal specifically, but they tend to have higher abundance and are more stable. Thirdly, we screened the CDR-containing protein domains that have a strong correlation with organism complexity. The CDR-containing domains tend to be evolutionarily young, or they changed from a domain without CDR to a CDR-containing domain during evolution. These results provide valuable new insights about the evolution and function of CDRs and protein domains.

NOT THAT RIGID MIDGETS AND NOT SO FLEXIBLE GIANTS: ON THE ABUNDANCE AND ROLES OF INTRINSIC DISORDER IN SHORT AND LONG PROTEINS

2012 ◽  
Vol 20 (04) ◽  
pp. 471-511 ◽  
Author(s):  
MARK HOWELL ◽  
RYAN GREEN ◽  
ALEXIS KILLEEN ◽  
LAMAR WEDDERBURN ◽  
VINCENT PICASCIO ◽  
...  
Keyword(s):  
Amino Acid ◽  
Intrinsically Disordered Proteins ◽  
Biological Activities ◽  
Intrinsic Disorder ◽  
Amino Acid Sequences ◽  
Disordered Proteins ◽  
Biological Functions ◽  
Intrinsically Disordered ◽  
Eukaryotic Proteins ◽  
Disordered Regions

Intrinsically disordered proteins or proteins with disordered regions are very common in nature. These proteins have numerous biological functions which are complementary to the biological activities of traditional ordered proteins. A noticeable difference in the amino acid sequences encoding long and short disordered regions was found and this difference was used in the development of length-dependent predictors of intrinsic disorder. In this study, we analyze the scaling of intrinsic disorder in eukaryotic proteins and investigate the presence of length-dependent functions attributed to proteins containing long disordered regions.

scholarly journals Why do eukaryotic proteins contain more intrinsically disordered regions?

2018 ◽  
Author(s):  
Walter Basile ◽  
Marco Salvatore ◽  
Claudio Bassot ◽  
Arne Elofsson
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Intrinsic Disorder ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Significant Difference ◽  
Eukaryotic Proteins ◽  
The Difference ◽  
Almost All ◽  
Disordered Regions

AbstractIntrinsic disorder is much more abundant in eukaryotic than in prokaryotic proteins. However, the reason behind this is unclear. It has been proposed that the disordered regions are functionally important for regulation in eukaryotes, but it has also been proposed that the difference is a result of lower selective pressure in eukaryotes. Almost all studies intrinsic disorder is predicted from the amino acid sequence of a protein. Therefore, there should exist an underlying difference in the amino acid distributions between eukaryotic and prokaryotic proteins causing the predicted difference in intrinsic disorder. To obtain a better understanding of why eukaryotic proteins contain more intrinsically disordered regions we compare proteins from complete eukaryotic and prokaryotic proteomes.Here, we show that the difference in intrinsic disorder origin from differences in the linker regions. Eukaryotic proteins have more extended linker regions and, in particular, the eukaryotic linker regions are more disordered. The average eukaryotic protein is about 500 residues long; it contains 250 residues in linker regions, of which 80 are disordered. In comparison, prokaryotic proteins are about 350 residues long and only have 100-110 residues in linker regions, and less than 10 of these are intrinsically disordered.Further, we show that there is no systematic increase in the frequency of disorder-promoting residues in eukaryotic linker regions. Instead, the difference in frequency of only three amino acids seems to lie behind the difference. The most significant difference is that eukaryotic linkers contain about 9% serine, while prokaryotic linkers have roughly 6.5%. Eukaryotic linkers also contain about 2% more proline and 2-3% fewer isoleucine residues. The reason why primarily these amino acids vary in frequency is not apparent, but it cannot be excluded that the difference is serine is related to the increased need for regulation through phosphorylation and that the proline difference is related to increase of eukaryotic specific repeats.

scholarly journals Conservation of Intrinsic Disorder in Protein Domains and Families:  II. Functions of Conserved Disorder

2006 ◽  
Vol 5 (4) ◽  
pp. 888-898 ◽  
Author(s):  
Jessica Walton Chen ◽  
Pedro Romero ◽  
Vladimir N. Uversky ◽  
A. Keith Dunker
Keyword(s):  
Protein Domains ◽  
Intrinsic Disorder

scholarly journals Functional Anthology of Intrinsic Disorder. 1. Biological Processes and Functions of Proteins with Long Disordered Regions

2007 ◽  
Vol 6 (5) ◽  
pp. 1882-1898 ◽  
Author(s):  
Hongbo Xie ◽  
Slobodan Vucetic ◽  
Lilia M. Iakoucheva ◽  
Christopher J. Oldfield ◽  
A. Keith Dunker ◽  
...  
Keyword(s):  
Intrinsic Disorder ◽  
Biological Processes ◽  
Disordered Regions

scholarly journals Role of “dual-personality” fragments in HEV adaptation—analysis of Y-domain region

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zoya Shafat ◽  
Anwar Ahmed ◽  
Mohammad K. Parvez ◽  
Shama Parveen
Keyword(s):  
Molecular Recognition ◽  
Functional Annotation ◽  
Rna Binding ◽  
Intrinsic Disorder ◽  
Hepatitis E ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Wide Range ◽  
Disordered Regions

Abstract Background Hepatitis E is a liver disease caused by the pathogen hepatitis E virus (HEV). The largest polyprotein open reading frame 1 (ORF1) contains a nonstructural Y-domain region (YDR) whose activity in HEV adaptation remains uncharted. The specific role of disordered regions in several nonstructural proteins has been demonstrated to participate in the multiplication and multiple regulatory functions of the viruses. Thus, intrinsic disorder of YDR including its structural and functional annotation was comprehensively studied by exploiting computational methodologies to delineate its role in viral adaptation. Results Based on our findings, it was evident that YDR contains significantly higher levels of ordered regions with less prevalence of disordered residues. Sequence-based analysis of YDR revealed it as a “dual personality” (DP) protein due to the presence of both structured and unstructured (intrinsically disordered) regions. The evolution of YDR was shaped by pressures that lead towards predominance of both disordered and regularly folded amino acids (Ala, Arg, Gly, Ile, Leu, Phe, Pro, Ser, Tyr, Val). Additionally, the predominance of characteristic DP residues (Thr, Arg, Gly, and Pro) further showed the order as well as disorder characteristic possessed by YDR. The intrinsic disorder propensity analysis of YDR revealed it as a moderately disordered protein. All the YDR sequences consisted of molecular recognition features (MoRFs), i.e., intrinsic disorder-based protein–protein interaction (PPI) sites, in addition to several nucleotide-binding sites. Thus, the presence of molecular recognition (PPI, RNA binding, and DNA binding) signifies the YDR’s interaction with specific partners, host membranes leading to further viral infection. The presence of various disordered-based phosphorylation sites further signifies the role of YDR in various biological processes. Furthermore, functional annotation of YDR revealed it as a multifunctional-associated protein, due to its susceptibility in binding to a wide range of ligands and involvement in various catalytic activities. Conclusions As DP are targets for regulation, thus, YDR contributes to cellular signaling processes through PPIs. As YDR is incompletely understood, therefore, our data on disorder-based function could help in better understanding its associated functions. Collectively, our novel data from this comprehensive investigation is the first attempt to delineate YDR role in the regulation and pathogenesis of HEV.

scholarly journals Arabidopsis Heat Stress-Induced Proteins Are Enriched in Electrostatically Charged Amino Acids and Intrinsically Disordered Regions

2018 ◽  
Vol 19 (8) ◽  
pp. 2276 ◽  
Author(s):  
David Alvarez-Ponce ◽  
Mario Ruiz-González ◽  
Francisco Vera-Sirera ◽  
Felix Feyertag ◽  
Miguel Perez-Amador ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
High Temperatures ◽  
Hydrophobic Interactions ◽  
Intrinsic Disorder ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Charged Amino Acids ◽  
Induced Proteins ◽  
Disordered Regions

Comparison of the proteins of thermophilic, mesophilic, and psychrophilic prokaryotes has revealed several features characteristic to proteins adapted to high temperatures, which increase their thermostability. These characteristics include a profusion of disulfide bonds, salt bridges, hydrogen bonds, and hydrophobic interactions, and a depletion in intrinsically disordered regions. It is unclear, however, whether such differences can also be observed in eukaryotic proteins or when comparing proteins that are adapted to temperatures that are more subtly different. When an organism is exposed to high temperatures, a subset of its proteins is overexpressed (heat-induced proteins), whereas others are either repressed (heat-repressed proteins) or remain unaffected. Here, we determine the expression levels of all genes in the eukaryotic model system Arabidopsis thaliana at 22 and 37 °C, and compare both the amino acid compositions and levels of intrinsic disorder of heat-induced and heat-repressed proteins. We show that, compared to heat-repressed proteins, heat-induced proteins are enriched in electrostatically charged amino acids and depleted in polar amino acids, mirroring thermophile proteins. However, in contrast with thermophile proteins, heat-induced proteins are enriched in intrinsically disordered regions, and depleted in hydrophobic amino acids. Our results indicate that temperature adaptation at the level of amino acid composition and intrinsic disorder can be observed not only in proteins of thermophilic organisms, but also in eukaryotic heat-induced proteins; the underlying adaptation pathways, however, are similar but not the same.

scholarly journals ‘Why genes in pieces?’—revisited

2019 ◽  
Vol 47 (10) ◽  
pp. 4970-4973 ◽  
Author(s):  
Ben Smithers ◽  
Matt Oates ◽  
Julian Gough
Keyword(s):  
General Property ◽  
Protein Domains ◽  
Protein Sequences ◽  
Data Sets ◽  
Domain Shuffling ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Evolution Of Proteins ◽  
Domain Exon ◽  
Disordered Regions

Abstract The alignment between the boundaries of protein domains and the boundaries of exons could provide evidence for the evolution of proteins via domain shuffling, but literature in the field has so far struggled to conclusively show this. Here, on larger data sets than previously possible, we do finally show that this phenomenon is indisputably found widely across the eukaryotic tree. In contrast, the alignment between exons and the boundaries of intrinsically disordered regions of proteins is not a general property of eukaryotes. Most interesting of all is the discovery that domain–exon alignment is much more common in recently evolved protein sequences than older ones.

scholarly journals Association between intrinsic disorder and serine/threonine phosphorylation in Mycobacterium tuberculosis

2014 ◽  
Author(s):  
Gajinder P Singh
Keyword(s):  
Protein Function ◽  
Substrate Recognition ◽  
Intrinsic Disorder ◽  
Protein Disorder ◽  
Phosphorylation Sites ◽  
Recognition Mechanism ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Regulate Protein ◽  
Disordered Regions

Serine/threonine phosphorylation is an important mechanism to regulate protein function. In eukaryotes phosphorylation occurs predominantly in intrinsically disordered regions of proteins. While serine/threonine phosphorylation and protein disorder are much less prevalent in prokaryotes, M. tuberculosis has both high serine/threonine phosphorylation and disorder. Here I show that, similar to eukaryotes, serine/threonine phosphorylation sites in M. tuberculosis are highly enriched in intrinsically disordered regions, indicating similarity in substrate recognition mechanism of eukaryotic and M. tuberculosis kinases. Serine/threonine phosphorylation has been linked to the pathogenicity and survival of M. tuberculosis, thus better understanding of how its kinases recognize their substrates could have important implications in understanding and controlling the biology of this deadly pathogen.

scholarly journals Multiple Nucleic Acid Binding Sites and Intrinsic Disorder of Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein: Implications for Ribonucleocapsid Protein Packaging

2008 ◽  
Vol 83 (5) ◽  
pp. 2255-2264 ◽  
Author(s):  
Chung-Ke Chang ◽  
Yen-Lan Hsu ◽  
Yuan-Hsiang Chang ◽  
Fa-An Chao ◽  
Ming-Chya Wu ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Severe Acute Respiratory Syndrome ◽  
Nucleocapsid Protein ◽  
Rna Binding ◽  
Intrinsic Disorder ◽  
Scattering Data ◽  
Nucleic Acid Binding ◽  
Structural Domains ◽  
N Protein ◽  
Disordered Regions

ABSTRACT The nucleocapsid protein (N) of the severe acute respiratory syndrome coronavirus (SARS-CoV) packages the viral genomic RNA and is crucial for viability. However, the RNA-binding mechanism is poorly understood. We have shown previously that the N protein contains two structural domains—the N-terminal domain (NTD; residues 45 to 181) and the C-terminal dimerization domain (CTD; residues 248 to 365)—flanked by long stretches of disordered regions accounting for almost half of the entire sequence. Small-angle X-ray scattering data show that the protein is in an extended conformation and that the two structural domains of the SARS-CoV N protein are far apart. Both the NTD and the CTD have been shown to bind RNA. Here we show that all disordered regions are also capable of binding to RNA. Constructs containing multiple RNA-binding regions showed Hill coefficients greater than 1, suggesting that the N protein binds to RNA cooperatively. The effect can be explained by the “coupled-allostery” model, devised to explain the allosteric effect in a multidomain regulatory system. Although the N proteins of different coronaviruses share very low sequence homology, the physicochemical features described above may be conserved across different groups of Coronaviridae. The current results underscore the important roles of multisite nucleic acid binding and intrinsic disorder in N protein function and RNP packaging.

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