scholarly journals Rational Design of Protein Stability: Effect of (2S,4R)-4-Fluoroproline on the Stability and Folding Pathway of Ubiquitin

PLoS ONE ◽  
2011 ◽  
Vol 6 (5) ◽  
pp. e19425 ◽  
Author(s):  
Maria D. Crespo ◽  
Marina Rubini
Keyword(s):  
Protein Stability ◽  
Rational Design ◽  
Folding Pathway ◽  
The Stability ◽  
Stability Effect

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.

Importance of Two Buried Salt Bridges in the Stability and Folding Pathway of Barnase†

Biochemistry ◽  
1996 ◽  
Vol 35 (21) ◽  
pp. 6786-6794 ◽  
Author(s):  
A. C. Tissot ◽  
S. Vuilleumier ◽  
A. R. Fersht
Keyword(s):  
Folding Pathway ◽  
Salt Bridges ◽  
The Stability

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 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.

scholarly journals VBP1 modulates Wnt/β-catenin signaling by mediating the stability of the transcription factors TCF/LEFs

2020 ◽  
Vol 295 (49) ◽  
pp. 16826-16839
Author(s):  
Haifeng Zhang ◽  
Xiaozhi Rong ◽  
Caixia Wang ◽  
Yunzhang Liu ◽  
Ling Lu ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Protein Stability ◽  
Signaling Pathway ◽  
Cultured Cells ◽  
Critical Role ◽  
Family Members ◽  
Von Hippel Lindau ◽  
T Cell Factor ◽  
Protein Levels ◽  
The Stability

The Wnt/β-catenin pathway is one of the major pathways that regulates embryonic development, adult homeostasis, and stem cell self-renewal. In this pathway, transcription factors T-cell factor and lymphoid enhancer factor (TCF/LEF) serve as a key switch to repress or activate Wnt target gene transcription by recruiting repressor molecules or interacting with the β-catenin effector, respectively. It has become evident that the protein stability of the TCF/LEF family members may play a critical role in controlling the activity of the Wnt/β-catenin signaling pathway. However, factors that regulate the stability of TCF/LEFs remain largely unknown. Here, we report that pVHL binding protein 1 (VBP1) regulates the Wnt/β-catenin signaling pathway by controlling the stability of TCF/LEFs. Surprisingly, we found that either overexpression or knockdown of VBP1 decreased Wnt/β-catenin signaling activity in both cultured cells and zebrafish embryos. Mechanistically, VBP1 directly binds to all four TCF/LEF family members and von Hippel-Lindau tumor-suppressor protein (pVHL). Either overexpression or knockdown of VBP1 increases the association between TCF/LEFs and pVHL and then decreases the protein levels of TCF/LEFs via proteasomal degradation. Together, our results provide mechanistic insights into the roles of VBP1 in controlling TCF/LEFs protein stability and regulating Wnt/β-catenin signaling pathway activity.

scholarly journals Context-dependent effects of proline residues on the stability and folding pathway of ubiquitin

2004 ◽  
Vol 271 (22) ◽  
pp. 4474-4484 ◽  
Author(s):  
Maria D. Crespo ◽  
Geoffrey W. Platt ◽  
Roger Bofill ◽  
Mark S. Searle
Keyword(s):  
Folding Pathway ◽  
Context Dependent ◽  
The Stability

Design of High Speed Railway Tunnel and its Construction Method in Abrupt Slope with Loose Rockmass

2014 ◽  
Vol 580-583 ◽  
pp. 1096-1099 ◽  
Author(s):  
Xiao Jun Zhou ◽  
Bo Jiang ◽  
Rui Yang ◽  
Chao Ning
Keyword(s):  
High Speed ◽  
Rational Design ◽  
Composite Fiber ◽  
Railway Tunnel ◽  
High Speed Railway ◽  
Working Face ◽  
Tunneling Method ◽  
Geological Conditions ◽  
The Stability ◽  
Tunnel Portal

This paper mainly deals with the structural design of high speed railway tunnel and its driving method in abrupt slope with loose rockmass, meanwhile summarizes the connection between tunnel portal and bridge abutment in loose rockmass according to complicated landform and geology. The anti-slide piles are adopted to retain the stability of abrupt slope near the tunnel portal. In order to eliminate the risk and cost in tunnel construction, four bench cut method is invented to satisfy the safe excavation of loose rockmass in the tunnel. Composite fiber rockbolt is also employed to keep the stability of working face while driving the tunnel. The innovative tunneling method presented in the paper can be applied to guide the rational design and economical construction of high speed railway tunnels in loose surrounding rock under harsh geological conditions.

Engineering of isoamylase: improvement of protein stability and catalytic efficiency through semi-rational design

2015 ◽  
Vol 43 (1) ◽  
pp. 3-12 ◽  
Author(s):  
Youran Li ◽  
Liang Zhang ◽  
Zhongyang Ding ◽  
Zhenghua Gu ◽  
Guiyang Shi
Keyword(s):  
Protein Stability ◽  
Rational Design ◽  
Catalytic Efficiency

Quantitative Control of C2S Crystal Transformation

2011 ◽  
Vol 121-126 ◽  
pp. 311-315
Author(s):  
Ming Zhao
Keyword(s):  
Sintering Temperature ◽  
Cement Clinker ◽  
Crystal Transformation ◽  
Chemical Impurities ◽  
Stabilizer Concentration ◽  
Rate Of Cooling ◽  
The Stability ◽  
Cement Clinkers ◽  
Stability Effect ◽  
Cooling Methods

Crystal transformation of dicalcium silicate (2CaO•SiO2, C2S) has influences on the microstructure, hydraulicity, and grindability of cement clinker. The transformation of β-C2S to γ-C2S can destroy the clinker nodule integrity by volume expansion due to the low density of the γ-phase. It can be used to pulverize cement clinkers for saving grinding energy, but the hydraulicity of γ-C2S is lower than β-C2S. Quantitative control of C2S crystal transformation could balance the energy saving and hydraulicity. The influences of sintering temperatures, cooling methods and chemical impurities on the transformation were investigated. The results show that the appropriate sintering temperature of γ-C2S was 1250～1500 °C, and the rate of cooling should not be higher than 500 °C/min to guarantee β-C2S transform to γ-C2S. Chemical impurities (Na2O, P2O5, B2O3, Cr2O3 and K2O) were stabilizers of β-C2S, which could prevent β-C2S transforming to γ-C2S. The stability effect was related to their concentrations. The characteristic concentrations of Na2O, P2O5, B2O3, Cr2O3 and K2O were approximately 1.2%, 0.3%, 0.3%, 1.0% and 1.5%, respectively. Above these concentrations, most of β-C2S could be stabilized rather than transforming to γ-C2S. In “transition zone”, C2S crystal transformation could be controlled quantitatively by adjusting the stabilizer concentration.

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