Faculty Opinions recommendation of Evaluation of sequence features from intrinsically disordered regions for the estimation of protein function.

2014 ◽  
Author(s):  
Vladimir Uversky
Keyword(s):  
Protein Function ◽  
Sequence Features ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Disordered Regions

scholarly journals Evaluation of Sequence Features from Intrinsically Disordered Regions for the Estimation of Protein Function

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e89890 ◽  
Author(s):  
Alok Sharma ◽  
Abdollah Dehzangi ◽  
James Lyons ◽  
Seiya Imoto ◽  
Satoru Miyano ◽  
...  
Keyword(s):  
Protein Function ◽  
Sequence Features ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Disordered Regions

scholarly journals Intrinsically disordered regions are abundant in simplexvirus proteomes and display signatures of positive selection

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Alessandra Mozzi ◽  
Diego Forni ◽  
Rachele Cagliani ◽  
Mario Clerici ◽  
Uberto Pozzoli ◽  
...  
Keyword(s):  
Positive Selection ◽  
Protein Function ◽  
Three Dimensional ◽  
New Host ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Human Proteins ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2 ◽  
Disordered Regions

Abstract Whereas the majority of herpesviruses co-speciated with their mammalian hosts, human herpes simplex virus 2 (HSV-2, genus Simplexvirus) most likely originated from the cross-species transmission of chimpanzee herpesvirus 1 to an ancestor of modern humans. We exploited the peculiar evolutionary history of HSV-2 to investigate the selective events that drove herpesvirus adaptation to a new host. We show that HSV-2 intrinsically disordered regions (IDRs)—that is, protein domains that do not adopt compact three-dimensional structures—are strongly enriched in positive selection signals. Analysis of viral proteomes indicated that a significantly higher portion of simplexvirus proteins is disordered compared with the proteins of other human herpesviruses. IDR abundance in simplexvirus proteomes was not a consequence of the base composition of their genomes (high G + C content). Conversely, protein function determines the IDR fraction, which is significantly higher in viral proteins that interact with human factors. We also found that the average extent of disorder in herpesvirus proteins tends to parallel that of their human interactors. These data suggest that viruses that interact with fast-evolving, disordered human proteins, in turn, evolve disordered viral interactors poised for innovation. We propose that the high IDR fraction present in simplexvirus proteomes contributes to their wider host range compared with other herpesviruses.

scholarly journals The contribution of intrinsically disordered regions to protein function, cellular complexity, and human disease

2016 ◽  
Vol 44 (5) ◽  
pp. 1185-1200 ◽  
Author(s):  
M. Madan Babu
Keyword(s):  
Protein Function ◽  
Human Disease ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Sequence Structure ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
The 1960S ◽  
Functional Versatility ◽  
Disordered Regions

In the 1960s, Christian Anfinsen postulated that the unique three-dimensional structure of a protein is determined by its amino acid sequence. This work laid the foundation for the sequence–structure–function paradigm, which states that the sequence of a protein determines its structure, and structure determines function. However, a class of polypeptide segments called intrinsically disordered regions does not conform to this postulate. In this review, I will first describe established and emerging ideas about how disordered regions contribute to protein function. I will then discuss molecular principles by which regulatory mechanisms, such as alternative splicing and asymmetric localization of transcripts that encode disordered regions, can increase the functional versatility of proteins. Finally, I will discuss how disordered regions contribute to human disease and the emergence of cellular complexity during organismal evolution.

scholarly journals Ubiquitin Interacting Motifs: Duality Between Structured and Disordered Motifs

2021 ◽  
Vol 8 ◽  
Author(s):  
Matteo Lambrughi ◽  
Emiliano Maiani ◽  
Burcu Aykac Fas ◽  
Gary S. Shaw ◽  
Birthe B. Kragelund ◽  
...  
Keyword(s):  
Protein Function ◽  
Chemical Shifts ◽  
Helical Structures ◽  
Conserved Sequence ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Multiple Partners ◽  
Common Motif ◽  
Dynamics Simulations ◽  
Disordered Regions

Ubiquitin is a small protein at the heart of many cellular processes, and several different protein domains are known to recognize and bind ubiquitin. A common motif for interaction with ubiquitin is the Ubiquitin Interacting Motif (UIM), characterized by a conserved sequence signature and often found in multi-domain proteins. Multi-domain proteins with intrinsically disordered regions mediate interactions with multiple partners, orchestrating diverse pathways. Short linear motifs for binding are often embedded in these disordered regions and play crucial roles in modulating protein function. In this work, we investigated the structural propensities of UIMs using molecular dynamics simulations and NMR chemical shifts. Despite the structural portrait depicted by X-crystallography of stable helical structures, we show that UIMs feature both helical and intrinsically disordered conformations. Our results shed light on a new class of disordered UIMs. This group is here exemplified by the C-terminal domain of one isoform of ataxin-3 and a group of ubiquitin-specific proteases. Intriguingly, UIMs not only bind ubiquitin. They can be a recruitment point for other interactors, such as parkin and the heat shock protein Hsc70-4. Disordered UIMs can provide versatility and new functions to the client proteins, opening new directions for research on their interactome.

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 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 Tandem repeats drive variation of intrinsically disordered regions in budding yeast

2018 ◽  
Author(s):  
Michael Babokhov ◽  
Bradley I. Reinfeld ◽  
Kevin Hackbarth ◽  
Yotam Bentov ◽  
Stephen M. Fuchs
Keyword(s):  
Protein Function ◽  
Copy Number ◽  
Tandem Repeats ◽  
Budding Yeast ◽  
Amino Acid Sequences ◽  
Length Variation ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Highly Correlated ◽  
Disordered Regions

AbstractCopy-number variation in tandem repeat coding regions is more prevalent in eukaryotic genomes than current literature suggests. We have reexamined the genomes of nearly 100 yeast strains looking to map regions of repeat variation. From this analysis we have identified that length variation is highly correlated to intrinsically disordered regions (IDRs). Furthermore, the majority of length variation is associated with tandem repeats. These repetitive regions are rich in homopolymeric amino acid sequences but nearly half of the variation comes from longer-repeating motifs. Comparisons of repeat copy number and sequence between strains of budding yeast as well as closely related fungi suggest selection for and conservation of IDR-related tandem repeats. In some instances, repeat variation has been demonstrated to mediate binding affinity, aggregation, and protein stability. With this analysis, we can identify proteins for which repeat variation may play conserved roles in modulating protein function.

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