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 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 Proteins of generalist and specialist pathogens differ in their amino acid composition

2018 ◽  
Vol 1 (4) ◽  
pp. e201800017 ◽  
Author(s):  
Luz P Blanco ◽  
Bryan L Payne ◽  
Felix Feyertag ◽  
David Alvarez-Ponce
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Composition ◽  
Host Range ◽  
Acid Composition ◽  
Secreted Proteins ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Cytoplasmic Proteins ◽  
Disordered Regions

Pathogens differ in their host specificities, with species infecting a unique host (specialist pathogens) and others having a wide host range (generalists). Molecular determinants of pathogen’s host range remain poorly understood. Secreted proteins of generalist pathogens are expected to have a broader range of intermolecular interactions (i.e., higher promiscuity) compared with their specialist counterparts. We hypothesize that this increased promiscuity of generalist secretomes may be based on an elevated content of primitive amino acids and intrinsically disordered regions, as these features are known to increase protein flexibility and interactivity. Here, we measure the proportion of primitive amino acids and percentage of intrinsically disordered residues in secreted, membrane, and cytoplasmic proteins from pathogens with different host specificity. Supporting our prediction, there is a significant general enrichment for primitive amino acids and intrinsically disordered regions in proteins from generalists compared to specialists, particularly among secreted proteins in prokaryotes. Our findings support our hypothesis that secreted proteins' amino acid composition and disordered content influence the pathogens' host range.

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 Proteome-wide signatures of function in highly diverged intrinsically disordered regions

2019 ◽  
Author(s):  
Taraneh Zarin ◽  
Bob Strome ◽  
Alex N Nguyen Ba ◽  
Simon Alberti ◽  
Julie D Forman-Kay ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequences ◽  
Functional Annotations ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Molecular Features ◽  
Primary Amino ◽  
Function Relationship ◽  
Disordered Regions

AbstractIntrinsically disordered regions make up a large part of the proteome, but the sequence-to-function relationship in these regions is poorly understood, in part because the primary amino acid sequences of these regions are poorly conserved in alignments. Here we use an evolutionary approach to detect molecular features that are preserved in the amino acid sequences of orthologous intrinsically disordered regions. We find that most disordered regions contain multiple molecular features that are preserved, and we define these as “evolutionary signatures” of disordered regions. We demonstrate that intrinsically disordered regions with similar evolutionary signatures can rescue functionin vivo,and that groups of intrinsically disordered regions with similar evolutionary signatures are strongly enriched for functional annotations and phenotypes. We propose that evolutionary signatures can be used to predict function for many disordered regions from their amino acid sequences.

scholarly journals Proteome-scale amino-acid resolution footprinting of protein-binding sites in the intrinsically disordered regions of the human proteome

2021 ◽  
Author(s):  
Caroline Benz ◽  
Muhammad Ali ◽  
Izabella Krystkowiak ◽  
Leandro Simonetti ◽  
Ahmed Sayadi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Interactions ◽  
Human Proteome ◽  
Cell Physiology ◽  
Protein Protein Interactions ◽  
Linear Motif ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Wide Range ◽  
Disordered Regions

Specific protein-protein interactions are central to all processes that underlie cell physiology. Numerous studies using a wide range of experimental approaches have identified tens of thousands of human protein-protein interactions. However, many interactions remain to be discovered, and low affinity, conditional and cell type-specific interactions are likely to be disproportionately under-represented. Moreover, for most known protein-protein interactions the binding regions remain uncharacterized. We previously developed proteomic peptide phage display (ProP-PD), a method for simultaneous proteome-scale identification of short linear motif (SLiM)-mediated interactions and footprinting of the binding region with amino acid resolution. Here, we describe the second-generation human disorderome (HD2), an optimized ProP-PD library that tiles all disordered regions of the human proteome and allows the screening of ~1,000,000 overlapping peptides in a single binding assay. We define guidelines for how to process, filter and rank the results and provide PepTools, a toolkit for annotation and analysis of identified hits. We uncovered 2,161 interaction pairs for 35 known SLiM-binding domains and confirmed a subset of 38 interactions by biophysical or cell-based assays. Finally, we show how the amino acid resolution binding site information can be used to pinpoint functionally important disease mutations and phosphorylation events in intrinsically disordered regions of the human proteome. The HD2 ProP-PD library paired with PepTools represents a powerful pipeline for unbiased proteome-wide discovery of SLiM-based interactions.

scholarly journals An amino acid at position 142 in nitrilase from Rhodococcus rhodochrous ATCC 33278 determines the substrate specificity for aliphatic and aromatic nitriles

2008 ◽  
Vol 415 (3) ◽  
pp. 401-407 ◽  
Author(s):  
Soo-Jin Yeom ◽  
Hye-Jung Kim ◽  
Jung-Kul Lee ◽  
Dong-Eun Kim ◽  
Deok-Kun Oh
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Hydrophobic Interactions ◽  
Electron System ◽  
Rhodococcus Rhodochrous ◽  
Aromatic Nitriles ◽  
Charged Amino Acids ◽  
Aromatic Substrates ◽  
In The Wild ◽  
Hydrolysis Of

Nitrilase from Rhodococcus rhodochrous ATCC 33278 hydrolyses both aliphatic and aromatic nitriles. Replacing Tyr-142 in the wild-type enzyme with the aromatic amino acid phenylalanine did not alter specificity for either substrate. However, the mutants containing non-polar aliphatic amino acids (alanine, valine and leucine) at position 142 were specific only for aromatic substrates such as benzonitrile, m-tolunitrile and 2-cyanopyridine, and not for aliphatic substrates. These results suggest that the hydrolysis of substrates probably involves the conjugated π-electron system of the aromatic ring of substrate or Tyr-142 as an electron acceptor. Moreover, the mutants containing charged amino acids such as aspartate, glutamate, arginine and asparagine at position 142 displayed no activity towards any nitrile, possibly owing to the disruption of hydrophobic interactions with substrates. Thus aromaticity of substrate or amino acid at position 142 in R. rhodochrous nitrilase is required for enzyme activity.

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 Proteome-wide signatures of function in highly diverged intrinsically disordered regions

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Taraneh Zarin ◽  
Bob Strome ◽  
Alex N Nguyen Ba ◽  
Simon Alberti ◽  
Julie D Forman-Kay ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequences ◽  
Functional Annotations ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Molecular Features ◽  
Primary Amino ◽  
Function Relationship ◽  
Disordered Regions

Intrinsically disordered regions make up a large part of the proteome, but the sequence-to-function relationship in these regions is poorly understood, in part because the primary amino acid sequences of these regions are poorly conserved in alignments. Here we use an evolutionary approach to detect molecular features that are preserved in the amino acid sequences of orthologous intrinsically disordered regions. We find that most disordered regions contain multiple molecular features that are preserved, and we define these as ‘evolutionary signatures’ of disordered regions. We demonstrate that intrinsically disordered regions with similar evolutionary signatures can rescue function in vivo, and that groups of intrinsically disordered regions with similar evolutionary signatures are strongly enriched for functional annotations and phenotypes. We propose that evolutionary signatures can be used to predict function for many disordered regions from their amino acid sequences.

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