scholarly journals Higher temperatures worsen the effects of mutations on protein stability

2020 ◽  
Author(s):  
Dimitrios - Georgios Kontopoulos ◽  
Ilias Patmanidis ◽  
Timothy G. Barraclough ◽  
Samraat Pawar
Keyword(s):  
Protein Stability ◽  
Adenylate Kinase ◽  
Computational Analysis ◽  
Thermal Adaptation ◽  
Moderately Thermophilic ◽  
Rate Of Molecular Evolution ◽  
Essential Enzyme ◽  
The Stability ◽  
Life On Earth ◽  
First Time

AbstractUnderstanding whether and how temperature increases alter the effects of mutations on protein stability is crucial for understanding the limits to thermal adaptation by organisms. Currently, it is generally assumed that the stability effects of mutations are independent of temperature. Yet, mutations should become increasingly destabilizing as temperature rises due to the increase in the energy of atoms. Here, by performing an extensive computational analysis on the essential enzyme adenylate kinase in prokaryotes, we show, for the first time, that mutations become more destabilizing with temperature both across and within species. Consistent with these findings, we find that substitution rates of prokaryotes decrease nonlinearly with temperature. Our results suggest that life on Earth likely originated in a moderately thermophilic and thermally fluctuating environment, and indicate that global warming should decrease the per-generation rate of molecular evolution of prokaryotes.

scholarly journals Reviving the Coordination Chemistry of Sulfonium Cations

2021 ◽  
Author(s):  
Ruiping Li ◽  
Nitsan Barel ◽  
Vasudevan Subramaniyan ◽  
Orit Cohen ◽  
Francoise Tibika ◽  
...  
Keyword(s):  
Coordination Chemistry ◽  
Computational Analysis ◽  
Acid Catalysis ◽  
Phosphine Ligands ◽  
Pincer Complexes ◽  
Full Characterization ◽  
Sulfonium Ions ◽  
The Stability ◽  
First Time

ABSTRACT: More than a century old, sulfonium ions are still intriguing species in the landscape of organic chemistry. On one hand they have found broad applications in organic synthesis and material science, but on the other hand, while isoelectronic to the ubiquitous tertiary phosphine ligands, their own coordination chemistry has been neglected for the last three decades. Here we report the synthesis and full characterization of the first Rh(I) and Pt(II) complexes of sul-fonium. Moreover, for the first time, the coordinating ability of an aromatic sulfonium has been established. A thorough computational analysis of the exceptionally short S-Rh bonds obtained attests for the strongly π-accepting nature of sul-fonium cations and places them among the best π-acceptor ligands available today. Our calculations also show that when embedded within a pincer framework their π-acidity is enhanced. Therefore, in addition to the stability and modularity that these frameworks offer, our pincer complexes might open the way for sulfonium cations to become powerful tools in π-acid catalysis.

Applicability of Instability Index for In vitro Protein Stability Prediction

2019 ◽  
Vol 26 (5) ◽  
pp. 339-347 ◽  
Author(s):  
Dilani G. Gamage ◽  
Ajith Gunaratne ◽  
Gopal R. Periyannan ◽  
Timothy G. Russell
Keyword(s):  
Protein Stability ◽  
Caulobacter Crescentus ◽  
Effect Of Temperature ◽  
Instability Index ◽  
Dipeptide Composition ◽  
Experimental Conditions ◽  
The Stability ◽  
Vitro Protein

Background: The dipeptide composition-based Instability Index (II) is one of the protein primary structure-dependent methods available for in vivo protein stability predictions. As per this method, proteins with II value below 40 are stable proteins. Intracellular protein stability principles guided the original development of the II method. However, the use of the II method for in vitro protein stability predictions raises questions about the validity of applying the II method under experimental conditions that are different from the in vivo setting. Objective: The aim of this study is to experimentally test the validity of the use of II as an in vitro protein stability predictor. Methods: A representative protein CCM (CCM - Caulobacter crescentus metalloprotein) that rapidly degrades under in vitro conditions was used to probe the dipeptide sequence-dependent degradation properties of CCM by generating CCM mutants to represent stable and unstable II values. A comparative degradation analysis was carried out under in vitro conditions using wildtype CCM, CCM mutants and two other candidate proteins: metallo-β-lactamase L1 and α -S1- casein representing stable, borderline stable/unstable, and unstable proteins as per the II predictions. The effect of temperature and a protein stabilizing agent on CCM degradation was also tested. Results: Data support the dipeptide composition-dependent protein stability/instability in wt-CCM and mutants as predicted by the II method under in vitro conditions. However, the II failed to accurately represent the stability of other tested proteins. Data indicate the influence of protein environmental factors on the autoproteolysis of proteins. Conclusion: Broader application of the II method for the prediction of protein stability under in vitro conditions is questionable as the stability of the protein may be dependent not only on the intrinsic nature of the protein but also on the conditions of the protein milieu.

scholarly journals A Novel Approach to Fabricate Foam Ceramics from Steel Slag

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Yu Zheng ◽  
Xudong Luo ◽  
Jinlong Yang ◽  
Wenlong Huo ◽  
Chi Kang
Keyword(s):  
Compressive Strength ◽  
Ph Value ◽  
Steel Slag ◽  
Raw Material ◽  
Solid Loading ◽  
Insulation Material ◽  
Ceramic Foams ◽  
Novel Approach ◽  
The Stability ◽  
First Time

A novel approach is used for fabricating steel slag foam ceramics based on the particle-stabilized foaming method. In this work, steel slag was used as the raw material and propyl gallate (PG) was used as the surface modifier. For the first time, steel slag ceramic foams were successfully fabricated based on particle-stabilized foams. The results show that the stability of the ceramic foams was closely related to the pH value and PG concentration. The porosity and compressive strength could be controlled by changing the solid loading of steel slag and sintering temperature. The porosity of steel slag foam ceramics ranged from 85.6% to 62.53%, and the compressive strength was from 1.74 MPa to 10.42 MPa. The thermal conductivity of steel slag foam ceramics was only 0.067 W (m·K)−1, which shows that it could be used as a thermal insulation material.

scholarly journals Temporal Stability and Biodiversity of Two Complex Antilisterial Cheese-Ripening Microbial Consortia

2003 ◽  
Vol 69 (7) ◽  
pp. 4012-4018 ◽  
Author(s):  
Ariel Maoz ◽  
Ralf Mayr ◽  
Siegfried Scherer
Keyword(s):  
Species Composition ◽  
Bacterial Species ◽  
Temporal Stability ◽  
Individual Characteristics ◽  
Microbial Consortia ◽  
Cheese Ripening ◽  
Safe Food ◽  
The Stability ◽  
The Individual ◽  
First Time

ABSTRACT The temporal stability and diversity of bacterial species composition as well as the antilisterial potential of two different, complex, and undefined microbial consortia from red-smear soft cheeses were investigated. Samples were collected twice, at 6-month intervals, from each of two food producers, and a total of 400 bacterial isolates were identified by Fourier-transform infrared spectroscopy and 16S ribosomal DNA sequence analysis. Coryneform bacteria represented the majority of the isolates, with certain species being predominant. In addition, Marinolactobacillus psychrotolerans, Halomonas venusta, Halomonas variabilis, Halomonas sp. (106 to 107 CFU per g of smear), and an unknown, gram-positive bacterium (107 to 108 CFU per g of smear) are described for the first time in such a consortium. The species composition of one consortium was quite stable over 6 months, but the other consortium revealed less diversity of coryneform species as well as less stability. While the first consortium had a stable, extraordinarily high antilisterial potential in situ, the antilisterial activity of the second consortium was lower and decreased with time. The cause for the antilisterial activity of the two consortia remained unknown but is not due to the secretion of soluble, inhibitory substances by the individual components of the consortium. Our data indicate that the stability over time and a potential antilisterial activity are individual characteristics of the ripening consortia which can be monitored and used for safe food production without artificial preservatives.

scholarly journals A glycine-specific N-degron pathway mediates the quality control of protein N-myristoylation

Science ◽  
2019 ◽  
Vol 365 (6448) ◽  
pp. eaaw4912 ◽  
Author(s):  
Richard T. Timms ◽  
Zhiqian Zhang ◽  
David Y. Rhee ◽  
J. Wade Harper ◽  
Itay Koren ◽  
...  
Keyword(s):  
Quality Control ◽  
Protein Stability ◽  
Protein Degradation ◽  
E3 Ligase ◽  
Cleavage Sites ◽  
Caspase Cleavage ◽  
E3 Ligases ◽  
Ring E3 Ligase ◽  
The Stability ◽  
Ring E3

The N-terminal residue influences protein stability through N-degron pathways. We used stability profiling of the human N-terminome to uncover multiple additional features of N-degron pathways. In addition to uncovering extended specificities of UBR E3 ligases, we characterized two related Cullin-RING E3 ligase complexes, Cul2ZYG11B and Cul2ZER1, that act redundantly to target N-terminal glycine. N-terminal glycine degrons are depleted at native N-termini but strongly enriched at caspase cleavage sites, suggesting roles for the substrate adaptors ZYG11B and ZER1 in protein degradation during apoptosis. Furthermore, ZYG11B and ZER1 were found to participate in the quality control of N-myristoylated proteins, in which N-terminal glycine degrons are conditionally exposed after a failure of N-myristoylation. Thus, an additional N-degron pathway specific for glycine regulates the stability of metazoan proteomes.

scholarly journals Crosstalk between β-catenin and WT1 signalling activity in acute myeloid leukemia

2021 ◽  
Author(s):  
Megan Payne ◽  
Olga Tsaponina ◽  
Gillian Caalim ◽  
Hayley Greenfield ◽  
Leanne Milton-Harris ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Myeloid Leukemia ◽  
Normal Development ◽  
Signal Transduction Pathway ◽  
Myeloid Cell ◽  
Wnt Signalling ◽  
Protein Protein Interactions ◽  
The Stability ◽  
First Time ◽  
Acute Myeloid

Wnt signalling is an evolutionary conserved signal transduction pathway heavily implicated in normal development and disease. The central mediator of this pathway, β-catenin, is frequently overexpressed, mislocalised and overactive in acute myeloid leukaemia (AML) where it mediates the establishment, maintenance and drug resistance of leukaemia stem cells. Critical to the stability, localisation and activity of β-catenin are the protein-protein interactions it forms, yet these are poorly defined in AML. We recently performed the first β-catenin interactome study in blood cells of any kind and identified a plethora of novel interacting partners. This study shows for the first time that β-catenin interacts with Wilms tumour protein (WT1), a protein frequently overexpressed and mutated in AML, in both myeloid cell lines and also primary AML samples. We demonstrate crosstalk between the signalling activity of these two proteins in myeloid cells, and show that modulation of either protein can affect expression of the other. Finally, we demonstrate that WT1 mutations frequently observed in AML can increase stabilise β-catenin and augment Wnt signalling output. This study has uncovered new context-dependent molecular interactions for β-catenin which could inform future therapeutic strategies to target this dysregulated molecule in AML.

scholarly journals Consistency and Stability of Motor Subtype Classifications in Patients With de novo Parkinson’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Jingru Ren ◽  
Chenxi Pan ◽  
Yuqian Li ◽  
Lanting Li ◽  
Ping Hua ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Classification Systems ◽  
Motor Symptoms ◽  
Chi Squared ◽  
Baseline Evaluation ◽  
The Stability ◽  
First Time ◽  
Non Motor Symptoms

ObjectivePatients with Parkinson’s disease (PD) are commonly classified into subtypes based on motor symptoms. The aims of the present study were to determine the consistency between PD motor subtypes, to assess the stability of PD motor subtypes over time, and to explore the variables influencing PD motor subtype stability.MethodsThis study was part of a longitudinal study of de novo PD patients at a single center. Based on three different motor subtype classification systems proposed by Jankovic, Schiess, and Kang, patients were respectively categorized as tremor-dominant/indeterminate/postural instability and gait difficulty (TD/indeterminate/PIGD), TDS/mixedS/akinetic-rigidS (ARS), or TDK/mixedK/ARK at baseline evaluation and then re-assessed 1 month later. Demographic and clinical characteristics were recorded at each evaluation. The consistency between subtypes at baseline evaluation was assessed using Cohen’s kappa coefficient (κ). Additional variables were compared between PD subtype groups using the two-sample t-test, Mann–Whitney U-test or Chi-squared test.ResultsOf 283 newly diagnosed, untreated PD patients, 79 were followed up at 1 month. There was fair agreement between the Jankovic, Schiess, and Kang classification systems (κS = 0.383 ± 0.044, κK = 0.360 ± 0.042, κSK = 0.368 ± 0.038). Among the three classification systems, the Schiess classification was the most stable and the Jankovic classification was the most unstable. The non-motor symptoms questionnaire (NMSQuest) scores differed significantly between PD patients with stable and unstable subtypes based on the Jankovic classification (p = 0.008), and patients with a consistent subtype had more severe NMSQuest scores than patients with an inconsistent subtype.ConclusionFair consistency was observed between the Jankovic, Schiess, and Kang classification systems. For the first time, non-motor symptoms (NMSs) scores were found to influence the stability of the TD/indeterminate/PIGD classification. Our findings support combining NMSs with motor symptoms to increase the effectiveness of PD subtypes.

scholarly journals Technical Note: Regularization performances with the error consistency method in the case of retrieved atmospheric profiles

2006 ◽  
Vol 6 (6) ◽  
pp. 13307-13321
Author(s):  
S. Ceccherini ◽  
C. Belotti ◽  
B. Carli ◽  
P. Raspollini ◽  
M. Ridolfi
Keyword(s):  
Regularization Parameter ◽  
Technical Note ◽  
Field Of View ◽  
Regularization Methods ◽  
Vertical Profiles ◽  
Vertical Resolution ◽  
Vertical Field ◽  
The Stability ◽  
First Time ◽  
Consistency Method

Abstract. The retrieval of concentration vertical profiles of atmospheric constituents from spectroscopic measurements is often an ill-conditioned problem and regularization methods are frequently used to improve its stability. Recently a new method, that provides a good compromise between precision and vertical resolution, was proposed to determine analytically the value of the regularization parameter. This method is applied for the first time to real measurements with its implementation in the operational retrieval code of the satellite limb-emission measurements of the MIPAS instrument and its performances are quantitatively analyzed. The adopted regularization improves the stability of the retrieval providing smooth profiles without major degradation of the vertical resolution. In the analyzed measurements the retrieval procedure provides a vertical resolution that, in the troposphere and low stratosphere, is smaller than the vertical field of view of the instrument.

scholarly journals Cellular ATP Levels Determine the Stability of a Nucleotide Kinase

2021 ◽  
Vol 8 ◽  
Author(s):  
Oliver Brylski ◽  
Puja Shrestha ◽  
Patricia Gnutt ◽  
David Gnutt ◽  
Jonathan Wolf Mueller ◽  
...  
Keyword(s):  
Protein Stability ◽  
Bound States ◽  
Atp Depletion ◽  
Aps Kinase ◽  
Cellular Processes ◽  
Atp Levels ◽  
Stability Change ◽  
Cell Stability ◽  
The Stability ◽  
Nucleotide Kinase

The energy currency of the cell ATP, is used by kinases to drive key cellular processes. However, the connection of cellular ATP abundance and protein stability is still under investigation. Using Fast Relaxation Imaging paired with alanine scanning and ATP depletion experiments, we study the nucleotide kinase (APSK) domain of 3′-phosphoadenosine-5′-phosphosulfate (PAPS) synthase, a marginally stable protein. Here, we show that the in-cell stability of the APSK is determined by ligand binding and directly connected to cellular ATP levels. The observed protein stability change for different ligand-bound states or under ATP-depleted conditions ranges from ΔGf0 = -10.7 to +13.8 kJ/mol, which is remarkable since it exceeds changes measured previously, for example upon osmotic pressure, cellular stress or differentiation. The results have implications for protein stability during the catalytic cycle of APS kinase and suggest that the cellular ATP level functions as a global regulator of kinase activity.

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