Multiparametric Analysis of Intrinsically Disordered Proteins: Looking at Intrinsic Disorder through Compound Eyes

2012 ◽  
Vol 84 (5) ◽  
pp. 2096-2104 ◽  
Author(s):  
Vladimir N. Uversky ◽  
A. Keith Dunker
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Intrinsic Disorder ◽  
Disordered Proteins ◽  
Compound Eyes ◽  
Intrinsically Disordered ◽  
Multiparametric Analysis

scholarly journals Roles, Characteristics, and Analysis of Intrinsically Disordered Proteins: A Minireview

Life ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 320
Author(s):  
Frederik Lermyte
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Neurological Disorders ◽  
Intrinsically Disordered Proteins ◽  
Intrinsic Disorder ◽  
Disordered Proteins ◽  
Dynamic Nature ◽  
Intrinsically Disordered ◽  
Unfolded State ◽  
Underlying Causes

In recent years, there has been a growing understanding that a significant fraction of the eukaryotic proteome is intrinsically disordered, and that these conformationally dynamic proteins play a myriad of vital biological roles in both normal and pathological states. In this review, selected examples of intrinsically disordered proteins are highlighted, with particular attention for a few which are relevant in neurological disorders and in viral infection. Next, the underlying causes for intrinsic disorder are discussed, along with computational methods used to predict whether a given amino acid sequence is likely to adopt a folded or unfolded state in solution. Finally, biophysical methods for the analysis of intrinsically disordered proteins will be discussed, as well as the unique challenges they pose in this context due to their highly dynamic nature.

scholarly journals Intrinsic disorder is an essential characteristic of components in the conserved circadian circuit

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Jacqueline F. Pelham ◽  
Jay C. Dunlap ◽  
Jennifer M. Hurley
Keyword(s):  
Circadian Clock ◽  
Neurospora Crassa ◽  
Mus Musculus ◽  
Intrinsically Disordered Proteins ◽  
Intrinsic Disorder ◽  
Cellular Systems ◽  
Disordered Proteins ◽  
Circadian Timing ◽  
Intrinsically Disordered ◽  
The Core

Abstract Introduction The circadian circuit, a roughly 24 h molecular feedback loop, or clock, is conserved from bacteria to animals and allows for enhanced organismal survival by facilitating the anticipation of the day/night cycle. With circadian regulation reportedly impacting as high as 80% of protein coding genes in higher eukaryotes, the protein-based circadian clock broadly regulates physiology and behavior. Due to the extensive interconnection between the clock and other cellular systems, chronic disruption of these molecular rhythms leads to a decrease in organismal fitness as well as an increase of disease rates in humans. Importantly, recent research has demonstrated that proteins comprising the circadian clock network display a significant amount of intrinsic disorder. Main body In this work, we focus on the extent of intrinsic disorder in the circadian clock and its potential mechanistic role in circadian timing. We highlight the conservation of disorder by quantifying the extent of computationally-predicted protein disorder in the core clock of the key eukaryotic circadian model organisms Drosophila melanogaster, Neurospora crassa, and Mus musculus. We further examine previously published work, as well as feature novel experimental evidence, demonstrating that the core negative arm circadian period drivers FREQUENCY (Neurospora crassa) and PERIOD-2 (PER2) (Mus musculus), possess biochemical characteristics of intrinsically disordered proteins. Finally, we discuss the potential contributions of the inherent biophysical principals of intrinsically disordered proteins that may explain the vital mechanistic roles they play in the clock to drive their broad evolutionary conservation in circadian timekeeping. Conclusion The pervasive conservation of disorder amongst the clock in the crown eukaryotes suggests that disorder is essential for optimal circadian timing from fungi to animals, providing vital homeostatic cellular maintenance and coordinating organismal physiology across phylogenetic kingdoms. Graphical abstract

scholarly journals Assemblages: Functional units formed by cellular phase separation

2014 ◽  
Vol 206 (5) ◽  
pp. 579-588 ◽  
Author(s):  
Jeffrey A. Toretsky ◽  
Peter E. Wright
Keyword(s):  
Phase Separation ◽  
Intrinsically Disordered Proteins ◽  
Intrinsic Disorder ◽  
Low Complexity ◽  
Disordered Proteins ◽  
Intracellular Space ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Disease States ◽  
Membrane Bound

The partitioning of intracellular space beyond membrane-bound organelles can be achieved with collections of proteins that are multivalent or contain low-complexity, intrinsically disordered regions. These proteins can undergo a physical phase change to form functional granules or other entities within the cytoplasm or nucleoplasm that collectively we term “assemblage.” Intrinsically disordered proteins (IDPs) play an important role in forming a subset of cellular assemblages by promoting phase separation. Recent work points to an involvement of assemblages in disease states, indicating that intrinsic disorder and phase transitions should be considered in the development of therapeutics.

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 Disorder Atlas: web-based software for the proteome-based interpretation of intrinsic disorder predictions

2016 ◽  
Author(s):  
Michael Vincent ◽  
Santiago Schnell
Keyword(s):  
Large Scale ◽  
Intrinsically Disordered Proteins ◽  
Three Dimensional ◽  
Intrinsic Disorder ◽  
Query Protein ◽  
Disordered Proteins ◽  
Dimensional Structure ◽  
Web Based ◽  
Intrinsically Disordered ◽  
Eukaryotic Proteomes

AbstractIntrinsically disordered proteins lack a stable three-dimensional structure under physiological conditions. While this property has gained considerable interest within the past two decades, disorder poses substantial challenges to experimental characterization efforts. In effect, numerous computational tools have been developed to predict disorder from primary sequences, however, interpreting the output of these algorithms remains a challenge. To begin to bridge this gap, we present Disorder Atlas, web-based software that facilitates the interpretation of intrinsic disorder predictions using proteome-based descriptive statistics. This service is also equipped to facilitate large-scale systematic exploratory searches for proteins encompassing disorder features of interest, and further allows users to browse the prevalence of multiple disorder features at the proteome level. As a result, Disorder Atlas provides a user-friendly tool that places algorithm-generated disorder predictions in the context of the proteome, thereby providing an instrument to compare the results of a query protein against predictions made for an entire population. Disorder Atlas currently supports ten eukaryotic proteomes and is freely available for non-commercial users at http://www.disorderatlas.org.

scholarly journals New technologies to analyse protein function: an intrinsic disorder perspective

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 101 ◽  
Author(s):  
Vladimir N. Uversky
Keyword(s):  
Protein Function ◽  
Intrinsically Disordered Proteins ◽  
New Technologies ◽  
Intrinsically Disordered Protein ◽  
Intrinsic Disorder ◽  
Disordered Proteins ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Protein Functions ◽  
Require Structure

Functions of intrinsically disordered proteins do not require structure. Such structure-independent functionality has melted away the classic rigid “lock and key” representation of structure–function relationships in proteins, opening a new page in protein science, where molten keys operate on melted locks and where conformational flexibility and intrinsic disorder, structural plasticity and extreme malleability, multifunctionality and binding promiscuity represent a new-fangled reality. Analysis and understanding of this new reality require novel tools, and some of the techniques elaborated for the examination of intrinsically disordered protein functions are outlined in this review.

Bioinformatics-based characterization of proteins related to SARS-CoV-2 using the Polarity Index Method® (PIM®) and Intrinsic Disorder Predisposition

2021 ◽  
Vol 18 ◽  
Author(s):  
Carlos Polanco ◽  
Vladimir N. Uversky ◽  
Guy W. Dayhoff II ◽  
Alberto Huberman ◽  
Thomas Buhse ◽  
...  
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Intrinsic Disorder ◽  
Cell Penetrating Peptides ◽  
Disordered Proteins ◽  
Structural Proteins ◽  
Public Health Issue ◽  
Index Method ◽  
Current Time ◽  
Intrinsically Disordered ◽  
Polarity Index

Background: The global outbreak of the 2019 novel Coronavirus Disease (COVID-19) caused by the infection with the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which appeared in China at the end of 2019, signifies a major public health issue at the current time. Objective: The objective of the present study is to characterize the physicochemical properties of the SARS-CoV-2 proteins at a residues level, and to generate a “bioinformatics fingerprint” in the form of a “PIM® profile” created for each sequence utilizing the Polarity Index Method® (PIM®), suitable for the identification of these proteins. Methods: Two different bioinformatics approaches were used to analyze sequence characteristics of these proteins at the residues level, an in-house bioinformatics system PIM®, and a set of the commonly used algorithms for the predic-tion of protein intrinsic disorder predisposition, such as PONDR® VLXT, PONDR® VL3, PONDR® VSL2, PONDR® FIT, IUPred_short and IUPred_long. The PIM® profile was generated for four SARS-CoV-2 structural proteins and compared with the corresponding profiles of the SARS-CoV-2 non-structural proteins, SARS-CoV-2 putative proteins, SARS-CoV proteins, MERS-CoV proteins, sets of bacterial, fungal, and viral proteins, cell-penetrating peptides, and a set of intrinsically disordered proteins. We also searched for the UniProt proteins with PIM® profiles similar to those of SARS-CoV-2 structural, non-structural, and putative proteins. Results: We show that SARS-CoV-2 structural, non-structural, and putative proteins are characterized by a unique PIM® profile. A total of 1736 proteins were identified from the 562,253 “reviewed” proteins from the UniProt database, whose PIM® profile was similar to that of the SARS-CoV-2 structural, non-structural, and putative proteins. Conclusion: The PIM® profile represents an important characteristic that might be useful for the identification of proteins similar to SARS-CoV-2 proteins.

scholarly journals Structural disorder and modular organization in Paramyxovirinae N and P

2003 ◽  
Vol 84 (12) ◽  
pp. 3239-3252 ◽  
Author(s):  
David Karlin ◽  
François Ferron ◽  
Bruno Canard ◽  
Sonia Longhi
Keyword(s):  
Measles Virus ◽  
Intrinsically Disordered Proteins ◽  
Intrinsic Disorder ◽  
Structural Disorder ◽  
Disordered Proteins ◽  
Modular Organization ◽  
Intrinsically Disordered ◽  
Physico Chemical ◽  
Chemical Concepts ◽  
Nucleoprotein N

The existence and extent of disorder within the replicative complex (N, P and the polymerase, L) of Paramyxovirinae were investigated, drawing on the discovery that the N-terminal moiety of the phosphoprotein (P) and the C-terminal moiety of the nucleoprotein (N) of measles virus are intrinsically unstructured. We show that intrinsic disorder is a widespread property within Paramyxovirinae N and P, using a combination of different computational approaches relying on different physico-chemical concepts. Notably, experimental support that has often gone unnoticed for most of the predictions has been found in the literature. Identification of disordered regions allows the unveiling of a common organization in all Paramyxovirinae P, which are composed of six modules defined on the basis of structure or sequence conservation. The possible functional significance of intrinsic disorder is discussed in the light of experimental data, which show that unstructured regions of P and N are involved in numerous interactions with several protein and protein–RNA partners. This study provides a contribution to the rather poorly investigated field of intrinsically disordered proteins and helps in targeting protein domains for structural studies.

scholarly journals Quantitative proteome-based guidelines for intrinsic disorder characterization

2015 ◽  
Author(s):  
Michael Vincent ◽  
Mark Whidden ◽  
Santiago Schnell
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Objective Assessment ◽  
Intrinsic Disorder ◽  
Disordered Proteins ◽  
Dimensional Structure ◽  
Sequence Length ◽  
Valuable Insight ◽  
Disorder Prediction ◽  
Intrinsically Disordered ◽  
Prediction Algorithms

AbstractIntrinsically disordered proteins fail to adopt a stable three-dimensional structure under physiological conditions. It is now understood that many disordered proteins are not dysfunctional, but instead engage in numerous cellular processes, including signaling and regulation. Disorder characterization from amino acid sequence relies on computational disorder prediction algorithms. While numerous large-scale investigations of disorder have been performed using these algorithms, and have offered valuable insight regarding the prevalence of protein disorder in many organisms, critical proteome-based descriptive statistical guidelines that would enable the objective assessment of intrinsic disorder in a protein of interest remain to be established. Here we present a quantitative characterization of numerous disorder features using a rigorous non-parametric statistical approach, providing expected values and percentile cutoffs for each feature in ten eukaryotic proteomes. Our estimates utilize multiple ab initio disorder prediction algorithms grounded on physicochemical principles. Furthermore, we present novel threshold values, specific to both the prediction algorithms and the proteomes, defining the longest primary sequence length in which the significance of a continuous disordered region can be evaluated on the basis of length alone. The guidelines presented here are intended to improve the interpretation of disorder content and continuous disorder predictions from the proteomic point of view.

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