Ubiquitin-Dependent Modification of Skeletal Muscle by the Parasitic Nematode, Trichinella spiralis

White, Rhiannon R.; Ponsford, Amy H.; Weekes, Michael P.; Rodrigues, Rachel B.; Ascher, David B.; Mol, Marco; Selkirk, Murray E.; Gygi, Steven P.; Sanderson, Christopher M.; Artavanis‐Tsakonas, Katerina

doi:10.1371/journal.ppat.1005977

Cited by 25 publications

(18 citation statements)

References 73 publications

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“…These single amino acid changes can readily disrupt the intricate network of intramolecular interactions, affecting how a protein folds, its stability, dynamics, and ultimately protein function. Beyond phenotypic outcomes, 1–22 it also has direct implications for their experimental study, protein engineering, 23,24 drug design, 25–30 and use in industrial processes 31 …”

Section: Introductionmentioning

confidence: 99%

DynaMut2: Assessing changes in stability and flexibility upon single and multiple point missense mutations

2020

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Predicting the effect of missense variations on protein stability and dynamics is important for understanding their role in diseases, and the link between protein structure and function. Approaches to estimate these changes have been proposed, but most only consider single‐point missense variants and a static state of the protein, with those that incorporate dynamics are computationally expensive. Here we present DynaMut2, a web server that combines Normal Mode Analysis (NMA) methods to capture protein motion and our graph‐based signatures to represent the wildtype environment to investigate the effects of single and multiple point mutations on protein stability and dynamics. DynaMut2 was able to accurately predict the effects of missense mutations on protein stability, achieving Pearson's correlation of up to 0.72 (RMSE: 1.02 kcal/mol) on a single point and 0.64 (RMSE: 1.80 kcal/mol) on multiple‐point missense mutations across 10‐fold cross‐validation and independent blind tests. For single‐point mutations, DynaMut2 achieved comparable performance with other methods when predicting variations in Gibbs Free Energy (ΔΔG) and in melting temperature (ΔTm). We anticipate our tool to be a valuable suite for the study of protein flexibility analysis and the study of the role of variants in disease. DynaMut2 is freely available as a web server and API at http://biosig.unimelb.edu.au/dynamut2.

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Section: Introductionmentioning

confidence: 99%

DynaMut2: Assessing changes in stability and flexibility upon single and multiple point missense mutations

2020

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“…Many efforts to computationally predict and model the effects of mutations on protein structure and function have started to help unravel the link between genotype and phenotype ( 6 – 16 ). Predicting the effects of mutations on altering protein–nucleic acid interactions, however, has been more intractable, with most approaches relying upon the use of force-fields, with limited success or scalability.…”

Section: Introductionmentioning

confidence: 99%

mCSM–NA: predicting the effects of mutations on protein–nucleic acids interactions

Pires

Ascher

2017

Nucleic Acids Research

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Over the past two decades, several computational methods have been proposed to predict how missense mutations can affect protein structure and function, either by altering protein stability or interactions with its partners, shedding light into potential molecular mechanisms giving rise to different phenotypes. Effectively and efficiently predicting consequences of mutations on protein–nucleic acid interactions, however, remained until recently a great and unmet challenge. Here we report an updated webserver for mCSM–NA, the only scalable method we are aware of capable of quantitatively predicting the effects of mutations in protein coding regions on nucleic acid binding affinities. We have significantly enhanced the original method by including a pharmacophore modelling and information of nucleic acid properties into our graph-based signatures, considering the reverse mutation and by using a refined, more reliable data set, based on a new release of the ProNIT database, which has significantly improved the reliability and applicability of the methodology. Our new predictive model was capable of achieving a correlation coefficient of up to 0.70 on cross-validation and 0.68 on blind-tests, outperforming its previous version. The server is freely available via a user-friendly web interface at: http://structure.bioc.cam.ac.uk/mcsm_na.

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“…Many parasites can also cause pathogenic changes accompanied by clinical symptoms. Pathological changes may occur at the site where the parasite is present, in which case they are referred to as direct local changes [45]. An example of this is the impact of parasites on tissues, which is observed in Trichinella spiralis larvae.…”

Section: State Of Knowledgementioning

confidence: 99%

“…An example of this is the impact of parasites on tissues, which is observed in Trichinella spiralis larvae. The larvae develop in the muscle cells causing loss of the active properties of the muscle [45]. Another example is the species Dioctophyme renale, which occurs in the renal pelvis, resulting in renal parenchyma atrophy [46,47] A species especially dangerous for humans is Entamoeba histolytica, which destroys the mucosa epithelium in the large intestine, leading to water absorption disorders, and is manifested by strong diarrhea [48][49][50][51].…”

Section: State Of Knowledgementioning

confidence: 99%

Toxicity of parasites and their unconventional use in medicine

Król¹,

Tomaszewska²,

Wróbel³

et al. 2019

Ann Agric Environ Med.

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Introduction. Over 300 species of parasites can possibly be passed on humans. Most of the parasitic infections are defined based on their pathogenicity; however, some positive effects of a parasite existence within the human body have recently been suggested. Beneficial outcomes of parasite infections might result from the production and release of metabolites, modification of host immune response or products uptake of the host. Objective. The aim of the study was a comprehensive analysis of a wide range of effects of parasites on the human body, including an overview of the toxic and positive effects. State of knowledge. In the light of the latest research presenting the unconventional use of parasites in medicine, the widely understood of their impact on the human body can also be considered in a positive context. Clinical cases from diseases caused by the toxic effects of parasites, as described in recent years, indicate that the problem of parasitic infections still persists. Despite a great deal of knowledge about the toxic effects of parasites on the human organism and, above all, despite the improvement in sanitary conditions, there is a resurgence of parasitic infections, as evidenced, e.g. by the examples presented in this review. Conclusions. The examples of positive effects of parasites presented so far give hope for the future in terms of fighting many diseases for which pharmacological treatment has not yet brought a positive effect. A better understanding of those processes might lead to the development of new methods of unconventional medical treatment.

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Ubiquitin-Dependent Modification of Skeletal Muscle by the Parasitic Nematode, Trichinella spiralis

Cited by 25 publications

References 73 publications

DynaMut2: Assessing changes in stability and flexibility upon single and multiple point missense mutations

DynaMut2: Assessing changes in stability and flexibility upon single and multiple point missense mutations

mCSM–NA: predicting the effects of mutations on protein–nucleic acids interactions

Toxicity of parasites and their unconventional use in medicine

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