Sequential Events in the Irreversible Thermal Denaturation of Human Brain-Type Creatine Kinase by Spectroscopic Methods

Gao, Yan-Song; Su, Jingtan; Yan, Yong‐Bin

doi:10.3390/ijms11072584

Cited by 15 publications

(12 citation statements)

References 53 publications

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“…It is possible that this minor transition correlated with the physiological functions of hCaf1. Similar body-temperature related pre-transitional conformational changes have also been characterized in several proteins such as hemoglobin, ribonuclease A and creatine kinase [28][29][30][31][32]. The two point mutations did not affect the thermal denaturation pathway of hCaf1, while slightly decreased the midpoint temperature of the main transition.…”

Section: The N-terminus Contributes To the Thermal Stability Of Hcaf1mentioning

confidence: 89%

The N-terminus modulates human Caf1 activity, structural stability and aggregation

Feng

Yan

2012

International Journal of Biological Macromolecules

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Section: The N-terminus Contributes To the Thermal Stability Of Hcaf1mentioning

confidence: 89%

The N-terminus modulates human Caf1 activity, structural stability and aggregation

Feng

Yan

2012

International Journal of Biological Macromolecules

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“…This difference may be because the study of contact order and folding speed has been limited to small proteins capable of in vitro refolding (28,(50)(51)(52)(53). Indeed, many proteins are unable to refold once denatured in vitro (54)(55)(56)(57)(58). Although the model proteins in this study are admittedly short in length, their properties can still generalize onto the characteristics of longer, real proteins.…”

Section: Folding Early On During Translationmentioning

confidence: 95%

Effect of protein structure on evolution of cotranslational folding

Zhao

Jacobs

Shakhnovich

2020

Preprint

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Cotranslational folding is expected to occur when the folding speed of the nascent chain is faster than the translation speed of the ribosome, but it is difficult to predict which proteins cotranslationally fold. Here, we simulate evolution of model proteins to investigate how native structure influences evolution of cotranslational folding. We developed a model that connects protein folding during and after translation to cellular fitness. Model proteins evolved improved folding speed and stability, with proteins adopting one of two strategies for folding quickly. Low contact order proteins evolve to fold cotranslationally. Such proteins adopt native conformations early on during the translation process, with each subsequently translated residue establishing additional native contacts. On the other hand, high contact order proteins tend not to be stable in their native conformations until the full chain is nearly extruded. We also simulated evolution of slowly translating codons, finding that slowing translation at certain positions enhances cotranslational folding. Finally, we investigated real protein structures using a previously published dataset that identified evolutionarily conserved rare codons in E. coli genes and associated such codons with cotranslational folding intermediates. We found that protein substructures preceding conserved rare codons tend to have lower contact orders, in line with our finding that lower contact order proteins are more likely to fold cotranslationally. Our work shows how evolutionary selection pressure can cause proteins with local contact topologies to evolve cotranslational folding. Statement of significanceSubstantial evidence exists for proteins folding as they are translated by the ribosome. Here we developed a biologically intuitive evolutionary model to show that avoiding premature protein degradation can be a sufficient evolutionary force to drive evolution of cotranslational folding. Furthermore, we find that whether a protein's native fold consists of more local or more nonlocal contacts affects whether cotranslational folding evolves. Proteins with local contact topologies are more likely to evolve cotranslational folding through nonsynonymous mutations that strengthen native contacts as well as through synonymous mutations that provide sufficient time for cotranslational folding intermediates to form.

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“…The emission spectra in the range of 300–400 nm were recorded using the excitation wavelength of 295 nm. The scans were done in triplicate, and the average results are presented [23]. …”

Section: Methodsmentioning

confidence: 99%

Improved scFv Anti-LOX-1 Binding Activity by Fusion with LOX-1-Binding Peptides

Xie

2017

BioMed Research International

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The oxidized low-density lipoprotein receptor-1 (LOX-1) targeted single-chain variable fragment (scFvs) is a promising molecule for the targeted delivery of imaging and therapeutic molecules of atherosclerotic diseases; however, its applications are limited by the inherent low antigen affinity. In this study, the three-dimensional (3D) model of the anti-LOX-1 scFv was constructed and its docking with the LOX-1 protein was developed. To improve the LOX-1-binding activity, the anti-LOX-1 scFv was designed to fuse with one of three LOX-1-binding heptapeptides, LTPATAI, FQTPPQL, and LSIPPKA, at its N-terminus and C-terminus and in the linker region, which have different LOX-1-binding interfaces with the anti-LOX-1 scFv analyzed by an array of computational approaches. These scFv/peptide fusions were constructed, successfully expressed in Brevibacillus choshinensis hosts, and purified by a two-step column purification process. The antigen binding activity, structural characteristics, thermal stability, and stability in serum of these fusion proteins were examined. Results showed that the scFv with N-terminal fusing peptides proteins demonstrated increased LOX-1-binding activity without decrease in stability. These findings will help increase the application efficacy of LOX-1 targeting scFv in LOX-1-based therapy.

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Sequential Events in the Irreversible Thermal Denaturation of Human Brain-Type Creatine Kinase by Spectroscopic Methods

Cited by 15 publications

References 53 publications

The N-terminus modulates human Caf1 activity, structural stability and aggregation

The N-terminus modulates human Caf1 activity, structural stability and aggregation

Effect of protein structure on evolution of cotranslational folding

Improved scFv Anti-LOX-1 Binding Activity by Fusion with LOX-1-Binding Peptides

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