scholarly journals Does folding determine protein configuration?

Nature ◽  
1994 ◽  
Vol 370 (6484) ◽  
pp. 13-13 ◽  
Author(s):  
John Maddox
2018 ◽  
Vol 10 (5) ◽  
pp. 4726-4736 ◽  
Author(s):  
Xuewei Fu ◽  
Chunhui Li ◽  
Yu Wang ◽  
Lucas Paul Kovatch ◽  
Louis Scudiero ◽  
...  

2016 ◽  
Vol 120 (4) ◽  
pp. 724-732 ◽  
Author(s):  
Sumera Tubasum ◽  
Magne Torbjörnsson ◽  
Dheerendra Yadav ◽  
Rafael Camacho ◽  
Gustaf Söderlind ◽  
...  

1957 ◽  
Vol 40 (4) ◽  
pp. 635-652 ◽  
Author(s):  
Georges Ungar ◽  
Emil Aschheim ◽  
Stacy Psychoyos ◽  
Dominick V. Romano

Changes in the configuration of proteins were studied by the modifications of the ultraviolet absorption of their alkaline solutions. These were expressed in terms of the ratio O.D.pH12/O.D.pH7, termed side-group ionization ratio (SGIR). This ratio showed two peaks; one at 300 to 305 mµ is known to correspond to the phenolic hydroxyl of tyrosine and another at 245 mµ seems to be caused by the ionization of the sulfhydryl group of cysteine. The SGIR of extracts from electrically stimulated nerve structures was found to be consistently and significantly higher than that of similar extracts from resting tissues. The phenomenon was observed in isolated nerves (frog and rat sciatic) stimulated in vitro and in the cerebral cortex of cats, dogs, and rats after stimulation of their afferents. The increase in SGIR was reversible if the stimulated structures were allowed to rest. Prolonged stimulation, in addition to causing structural changes, also caused breakdown of proteins and the appearance of proteolytic activity. The latter, studied on a synthetic substrate, could be detected even after shorter stimuli, together with configurational changes but without proteolysis. The structural changes detected with the spectrophotometric method are closely related to reversible denaturation as produced by urea. The changes probably involve rupture of hydrogen bonds which loosens the protein molecule and perhaps changes its affinity for different ions. It is possible that such a process may play a role in the mechanism of excitation.


2020 ◽  
Vol 2020 (1) ◽  
pp. 219-224
Author(s):  
Nicholas F Brazeau ◽  
Kara J Levinson ◽  
Asher Schranz ◽  
Kara A Moser ◽  
Ian Hollis ◽  
...  

Abstract Daptomycin (DAP) is key in treating multidrug-resistant Staphylococcus infections. Diminished susceptibility to DAP is emerging among Staphylococcus epidermidis strains although mechanisms for non-susceptibility (NS) remain poorly understood. We report a case of persistent S. epidermidis bacteremia in which loss of DAP susceptibility arose during prolonged treatment. Whole genome sequencing identified two mutations, Q371del and P415L, in a single-affected gene, WalK, that coincided with the emergence of DAP-NS. Protein modeling of the mutations predicted a disruption of WalK protein configuration. The emergence of mutations in a single-gene during DAP exposure raises concerns in an era of increasingly treatment-resistant infections. Lay summary: Daptomycin is an important antibiotic for fighting Staphylococcus infections. We identified variants in the WalK gene that were coincident with resistance in a clinical Staphylococcus epidermidis infection. Clinicians, hospital epidemiologists, and microbiology laboratories need to be aware of the potential for the evolution of drug resistance during prolonged daptomycin therapy.


2019 ◽  
Author(s):  
Jeffrey B.S. Gaither ◽  
Grant E. Lammi ◽  
James L. Li ◽  
David M. Gordon ◽  
Harkness C. Kuck ◽  
...  

ABSTRACTBackgroundIn most organisms the structure of an mRNA molecule is crucial in determining speed of translation, half-life, splicing propensities and final protein configuration. Synonymous variants which distort this wildtype mRNA structure may be pathogenic as a consequence. However, current clinical guidelines classify synonymous or “silent” single nucleotide variants (sSNVs) as largely benign unless a role in RNA splicing can be demonstrated.ResultsWe developed novel software to conduct a global transcriptome study in which RNA folding statistics were computed for 469 million SNVs in 45,800 transcripts using an Apache Spark implementation of ViennaRNA in the cloud. Focusing our analysis on the subset of 17.9 million sSNVs, we discover that variants predicted to disrupt mRNA structure have lower rates of incidence in the human population. Given that the community lacks tools to evaluate the potential pathogenic impact of sSNVs, we introduce a “Structural Predictivity Index” (SPI) to quantify this constraint due to mRNA structure.ConclusionsOur findings support the hypothesis that sSNVs may play a role in genetic disorders due to their effects on mRNA structure. Our RNA-folding scores provide a means of gauging the structural constraint operating on any sSNV in the human genome. Given that the majority of patients with rare or as yet to be diagnosed disease lack a molecular diagnosis, these scores have the potential to enable discovery of novel genetic etiologies. Our RNA Stability Pipeline as well as ViennaRNA structural metrics and SPI scores for all human synonymous variants can be downloaded from GitHub https://github.com/nch-igm/rna-stability.


Sign in / Sign up

Export Citation Format

Share Document