Book ChapterDOI
Functions of intrinsically disordered proteins through evolutionary lenses.
TLDR
In this article, the authors give an overview of the different types of evolutionary behavior of disordered proteins and associated functions in normal and disease settings in both disease and normal settings. But, different evolutionary rules apply for the group of intrinsically disordered regions and proteins (IDR/IDPs) that exist as an ensemble of fluctuating conformations.Abstract:
Protein sequences are the result of an evolutionary process that involves the balancing act of experimenting with novel mutations and selecting out those that have an undesirable functional outcome. In the case of globular proteins, the function relies on a well-defined conformation, therefore, there is a strong evolutionary pressure to preserve the structure. However, different evolutionary rules might apply for the group of intrinsically disordered regions and proteins (IDR/IDPs) that exist as an ensemble of fluctuating conformations. The function of IDRs can directly originate from their disordered state or arise through different types of molecular recognition processes. There is an amazing variety of ways IDRs can carry out their functions, and this is also reflected in their evolutionary properties. In this chapter we give an overview of the different types of evolutionary behavior of disordered proteins and associated functions in normal and disease settings.read more
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Journal ArticleDOI
Characterization of intrinsically disordered regions in proteins informed by human genetic diversity
Shehab S. Ahmed,Zaara T. Rifat,Ruchi Lohia,Arthur J. Campbell,A. Keith Dunker,Mohammad Sohel Rahman,Sumaiya Iqbal +6 more
TL;DR: This study presents a novel approach to assign functional importance to IDRs by leveraging the wealth of available genetic data, which will aid in a deeper understating of the role of IDRs in biological processes and disease mechanisms.
Journal ArticleDOI
The opportunities and challenges posed by the new generation of deep learning-based protein structure predictors.
TL;DR: The early 2020s saw the advent of a new generation of deep learning-based protein structure prediction tools that offer the potential to predict structures based on any number of protein sequences as mentioned in this paper .
Journal ArticleDOI
The Cynosure of CtBP: Evolution of a Bilaterian Transcriptional Corepressor
Ana-Maria Raicu,Dhruva Kadiyala,Madeline Niblock,Aanchal Kumar Jain,Yahui Yang,Kalynn M. Bird,Kayla Bertholf,Akshay Seenivasan,David N. Arnosti +8 more
TL;DR: A comparative phylogenetic study shows that CtBP is a bilaterian innovation whose CTD of about 100 residues is present in almost all orthologs, and highlights the rich regulatory potential of this previously unstudied domain of a central transcriptional regulator.
Journal ArticleDOI
Ten Plastomes of Crassula (Crassulaceae) and Phylogenetic Implications
Hengwu Ding,Shiyun Han,Yuan Ye,D. Bi,Sijia Zhang,Ran Yi,Jinming Gao,Jianke Yang,Long-Fei Wu,Xianzhao Kan +9 more
TL;DR: In this article , the second largest genus in the family Crassulaceae, Crassula L. is the second most common genus in angiosperms, but variable in size, gene content, and evolutionary rates of genes.
Journal ArticleDOI
The DYW domain of RARE1 plays an indispensable role in regulating accD-C794 RNA editing in Arabidopsis thaliana.
TL;DR: In this paper , the authors investigate the correlation between Arabidopsis pentatricopeptide repeat (PPR) proteins and their respective DYW domain functions in RNA editing of accD-C794.
References
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Journal ArticleDOI
Comprehensive review of methods for prediction of intrinsic disorder and its molecular functions.
TL;DR: This work is the first to cover predictors of molecular functions of disorder, including 13 methods that focus on disordered linkers and disordered protein–protein, protein–RNA, and protein–DNA binding regions, and overview their predictive models, usability, and predictive performance.
Journal ArticleDOI
IUPred3: prediction of protein disorder enhanced with unambiguous experimental annotation and visualization of evolutionary conservation
Abstract: Intrinsically disordered proteins and protein regions (IDPs/IDRs) exist without a single well-defined conformation. They carry out important biological functions with multifaceted roles which is also reflected in their evolutionary behavior. Computational methods play important roles in the characterization of IDRs. One of the commonly used disorder prediction methods is IUPred, which relies on an energy estimation approach. The IUPred web server takes an amino acid sequence or a Uniprot ID/accession as an input and predicts the tendency for each amino acid to be in a disordered region with an option to also predict context-dependent disordered regions. In this new iteration of IUPred, we added multiple novel features to enhance the prediction capabilities of the server. First, learning from the latest evaluation of disorder prediction methods we introduced multiple new smoothing functions to the prediction that decreases noise and increases the performance of the predictions. We constructed a dataset consisting of experimentally verified ordered/disordered regions with unambiguous annotations which were added to the prediction. We also introduced a novel tool that enables the exploration of the evolutionary conservation of protein disorder coupled to sequence conservation in model organisms. The web server is freely available to users and accessible at https://iupred3.elte.hu.
Journal ArticleDOI
Bringing order to protein disorder through comparative genomics and genetic interactions
Jeremy Bellay,Sangjo Han,Magali Michaut,TaeHyung Kim,Michael Costanzo,Brenda J. Andrews,Charles Boone,Gary D. Bader,Chad L. Myers,Philip M. Kim +9 more
TL;DR: The clear and distinct functional association of flexible and constrained disorder will allow for new approaches and more specific algorithms for disorder detection in a functional context and demonstrate clear evolutionary selection of protein disorder with little selection on primary structure.
Journal ArticleDOI
Protein disorder — a breakthrough invention of evolution?
Avner Schlessinger,Christian Schaefer,Esmeralda Vicedo,Markus Schmidberger,Marco Punta,Burkhard Rost +5 more
TL;DR: It is more useful to picture disorder as a distinct phenomenon in structural biology than as an extreme example of protein flexibility, and it seems advantageous to portray the universe of all possible proteins in terms of two main types: well-structured, disordered.
Journal ArticleDOI
Critical assessment of protein intrinsic disorder prediction
TL;DR: The Critical Assessment of protein Intrinsic Disorder prediction (CAID) experiment was established as a community-based blind test to determine the state of the art in prediction of intrinsically disordered regions and the subset of residues involved in binding as mentioned in this paper.