scholarly journals Random coil chemical shifts for serine, threonine and tyrosine phosphorylation over a broad pH range

2019 ◽  
Vol 73 (12) ◽  
pp. 713-725 ◽  
Author(s):  
Ruth Hendus-Altenburger ◽  
Catarina B. Fernandes ◽  
Katrine Bugge ◽  
Micha B. A. Kunze ◽  
Wouter Boomsma ◽  
...  
Keyword(s):  
Chemical Shift ◽  
Secondary Structure ◽  
Intrinsically Disordered Proteins ◽  
Chemical Shifts ◽  
Random Coil ◽  
Disordered Proteins ◽  
Phosphoryl Group ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Secondary Chemical

Abstract Phosphorylation is one of the main regulators of cellular signaling typically occurring in flexible parts of folded proteins and in intrinsically disordered regions. It can have distinct effects on the chemical environment as well as on the structural properties near the modification site. Secondary chemical shift analysis is the main NMR method for detection of transiently formed secondary structure in intrinsically disordered proteins (IDPs) and the reliability of the analysis depends on an appropriate choice of random coil model. Random coil chemical shifts and sequence correction factors were previously determined for an Ac-QQXQQ-NH2-peptide series with X being any of the 20 common amino acids. However, a matching dataset on the phosphorylated states has so far only been incompletely determined or determined only at a single pH value. Here we extend the database by the addition of the random coil chemical shifts of the phosphorylated states of serine, threonine and tyrosine measured over a range of pH values covering the pKas of the phosphates and at several temperatures (www.bio.ku.dk/sbinlab/randomcoil). The combined results allow for accurate random coil chemical shift determination of phosphorylated regions at any pH and temperature, minimizing systematic biases of the secondary chemical shifts. Comparison of chemical shifts using random coil sets with and without inclusion of the phosphoryl group, revealed under/over estimations of helicity of up to 33%. The expanded set of random coil values will improve the reliability in detection and quantification of transient secondary structure in phosphorylation-modified IDPs.

scholarly journals CheSPI: Chemical shift Secondary structure Population Inference

2021 ◽  
Author(s):  
Jakob Toudahl Nielsen ◽  
Frans A.A. Mulder
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Chemical Shifts ◽  
Protein Structures ◽  
Random Coil ◽  
Disordered Proteins ◽  
Residual Structure ◽  
Intrinsically Disordered ◽  
Population Inference ◽  
Local Protein Structure ◽  
Structural Classes

AbstractNMR chemical shifts (CSs) are delicate reporters of local protein structure, and recent advances in random coil CS (RCCS) prediction and interpretation now offer the compelling prospect of inferring small populations of structure from small deviations from RCCSs. Here, we present CheSPI, a simple and efficient method that provides unbiased and sensitive aggregate measures of local structure and disorder. It is demonstrated that CheSPI can predict even very small amounts of residual structure and robustly delineate subtle differences into four structural classes for intrinsically disordered proteins. For structured regions and proteins, CheSPI can assign up to eight structural classes, which coincide with the well-known DSSP classification. The program is freely available, and can either be invoked from URL www.protein-nmr.org as a web implementation, or run locally from command line as a python program. CheSPI generates comprehensive numeric and graphical output for intuitive annotation and visualization of protein structures. A number of examples are provided.

Prediction of the Disordered Regions of Intrinsically Disordered Proteins Based on the Molecular Functions

2020 ◽  
Vol 27 (4) ◽  
pp. 279-286 ◽  
Author(s):  
WeiXia Xie ◽  
Yong E. Feng
Keyword(s):  
Chemical Shift ◽  
Intrinsically Disordered Proteins ◽  
Chemical Shifts ◽  
Disordered Proteins ◽  
Dimensional Structure ◽  
Support Vector ◽  
Functional Sites ◽  
Intrinsically Disordered ◽  
Molecular Functions ◽  
Disordered Regions

Background: Intrinsically disordered proteins lack a well-defined three dimensional structure under physiological conditions while possessing the essential biological functions. They take part in various physiological processes such as signal transduction, transcription and posttranslational modifications and etc. The disordered regions are the main functional sites for intrinsically disordered proteins. Therefore, the research of the disordered regions has become a hot issue. Objective: In this paper, our motivation is to analysis of the features of disordered regions with different molecular functions and predict of different disordered regions using valid features. Methods: In this article, according to the different molecular function, we firstly divided intrinsically disordered proteins into six classes in DisProt database. Then, we extracted four features using bioinformatics methods, namely, Amino Acid Index (AAIndex), codon frequency (Codon), three kinds of protein secondary structure compositions (3PSS) and Chemical Shifts (CSs), and used these features to predict the disordered regions of the different functions by Support Vector Machine (SVM). Results: The best overall accuracy was 99.29% using the chemical shift (CSs) as feature. In feature fusion, the overall accuracy can reach 88.70% by using CSs+AAIndex as features. The overall accuracy was up to 86.09% by using CSs+AAIndex+Codon+3PSS as features. Conclusion: We predicted and analyzed the disordered regions based on the molecular functions. The results showed that the prediction performance can be improved by adding chemical shifts and AAIndex as features, especially chemical shifts. Moreover, the chemical shift was the most effective feature in the prediction. We hoped that our results will be constructive for the study of intrinsically disordered proteins.

scholarly journals Structure-Function Insights of Jaburetox and Soyuretox: Novel Intrinsically Disordered Polypeptides Derived from Plant Ureases

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5338
Author(s):  
Matheus V. Coste Grahl ◽  
Fernanda Cortez Lopes ◽  
Anne H. Souza Martinelli ◽  
Celia R. Carlini ◽  
Leonardo L. Fruttero
Keyword(s):  
Secondary Structure ◽  
Lipid Membranes ◽  
Intrinsically Disordered Proteins ◽  
Biological Activities ◽  
3D Structure ◽  
Disordered Proteins ◽  
Recombinant Peptide ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Ubiquitous Urease

Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) do not have a stable 3D structure but still have important biological activities. Jaburetox is a recombinant peptide derived from the jack bean (Canavalia ensiformis) urease and presents entomotoxic and antimicrobial actions. The structure of Jaburetox was elucidated using nuclear magnetic resonance which reveals it is an IDP with small amounts of secondary structure. Different approaches have demonstrated that Jaburetox acquires certain folding upon interaction with lipid membranes, a characteristic commonly found in other IDPs and usually important for their biological functions. Soyuretox, a recombinant peptide derived from the soybean (Glycine max) ubiquitous urease and homologous to Jaburetox, was also characterized for its biological activities and structural properties. Soyuretox is also an IDP, presenting more secondary structure in comparison with Jaburetox and similar entomotoxic and fungitoxic effects. Moreover, Soyuretox was found to be nontoxic to zebra fish, while Jaburetox was innocuous to mice and rats. This profile of toxicity affecting detrimental species without damaging mammals or the environment qualified them to be used in biotechnological applications. Both peptides were employed to develop transgenic crops and these plants were active against insects and nematodes, unveiling their immense potentiality for field applications.

Sequence Specificity Despite Intrinsic Disorder: How a Disease-Associated Val/Met Polymorphism Shifts Tertiary Interactions in a Long Disordered Protein

2019 ◽  
Author(s):  
Ruchi Lohia ◽  
Reza Salari ◽  
Grace Brannigan
Keyword(s):  
Secondary Structure ◽  
Electrostatic Interactions ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Sequence Specificity ◽  
Intrinsically Disordered ◽  
Specific Effects ◽  
Heterogeneous Polymer ◽  
Non Local ◽  
Dynamics Simulations

<div>The role of electrostatic interactions and mutations that change charge states in intrinsically disordered proteins (IDPs) is well-established, but many disease-associated mutations in IDPs are charge-neutral. The Val66Met single nucleotide polymorphism (SNP) encodes a hydrophobic-to-hydrophobic mutation at the midpoint of the prodomain of precursor brain-derived neurotrophic factor (BDNF), one of the earliest SNPs to be associated with neuropsychiatric disorders, for which the underlying molecular mechanism is unknown. Here we report on over 250 μs of fully-atomistic, explicit solvent, temperature replica exchange molecular dynamics simulations of the 91 residue BDNF prodomain, for both the V66 and M66 sequence.</div><div>The simulations were able to correctly reproduce the location of both local and non-local secondary changes due to the Val66Met mutation when compared with NMR spectroscopy. We find that the local structure change is mediated via entropic and sequence specific effects. We show that the highly disordered prodomain can be meaningfully divided into domains based on sequence alone. Monte Carlo simulations of a self-excluding heterogeneous polymer, with monomers representing each domain, suggest the sequence would be effectively segmented by the long, highly disordered polyampholyte near the sequence midpoint. This is qualitatively consistent with observed interdomain contacts within the BDNF prodomain, although contacts between the two segments are enriched relative to the self-excluding polymer. The Val66Met mutation increases interactions across the boundary between the two segments, due in part to a specific Met-Met interaction with a Methionine in the other segment. This effect propagates to cause the non-local change in secondary structure around the second methionine, previously observed in NMR. The effect is not mediated simply via changes in inter-domain contacts but is also dependent on secondary structure formation around residue 66, indicating a mechanism for secondary structure coupling in disordered proteins. </div>

Sign in / Sign up

Export Citation Format

Share Document