scholarly journals The History of Pertussis Toxin

Toxins ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 623
Author(s):  
Camille Locht ◽  
Rudy Antoine
Keyword(s):  
Single Molecule ◽  
Pertussis Toxin ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Protective Antigen ◽  
Whooping Cough ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
History Of ◽  
New Generation

Besides the typical whooping cough syndrome, infection with Bordetella pertussis or immunization with whole-cell vaccines can result in a wide variety of physiological manifestations, including leukocytosis, hyper-insulinemia, and histamine sensitization, as well as protection against disease. Initially believed to be associated with different molecular entities, decades of research have provided the demonstration that these activities are all due to a single molecule today referred to as pertussis toxin. The three-dimensional structure and molecular mechanisms of pertussis toxin action, as well as its role in protective immunity have been uncovered in the last 50 years. In this article, we review the history of pertussis toxin, including the paradigm shift that occurred in the 1980s which established the pertussis toxin as a single molecule. We describe the role molecular biology played in the understanding of pertussis toxin action, its role as a molecular tool in cell biology and as a protective antigen in acellular pertussis vaccines and possibly new-generation vaccines, as well as potential therapeutical applications.

Characterization of an A-type cyclin-dependent kinase gene from Dendrobium candidum

Biologia ◽  
2012 ◽  
Vol 67 (2) ◽  
Author(s):  
Gang Zhang ◽  
Chao Song ◽  
Ming-Ming Zhao ◽  
Biao Li ◽  
Shun-Xing Guo
Keyword(s):  
Molecular Mechanisms ◽  
Three Dimensional ◽  
Postembryonic Development ◽  
Kinase Domain ◽  
Dimensional Structure ◽  
Pcr Analysis ◽  
Kinase Gene ◽  
Multiple Sequence ◽  
Dendrobium Candidum ◽  
Rapid Amplification

AbstractCyclin-dependent kinases (CDKs) play an essential role in cell cycle regulation during the embryonic and postembryonic development of organisms. To better understand the molecular mechanisms of CDKs involved in embryogenesis regulation in the endangered medicinal plant Dendrobium candidum Wall. ex Lindl., a 1229-bp full-length cDNA of an A-type CDK gene, Denca;CDKA;1, was identified using 3′ rapid amplification of cDNA end (RACE) PCR. Denca;CDKA;1 was predicted to encode a 294 amino acid residue-long protein of 33.76 kDa with an isoelectric point of 7.72. The deduced Denca;CDKA;1 protein contained a conserved serine/threonine-protein kinase domain (S-TKc) and a canonical cyclinbinding “PSTAIRE” motif. Multiple sequence alignment indicated that members of CDKA family from various plants exhibited a high degree of sequence identity ranging from 82% to 93%. A neighbor-joining phylogenetic tree showed that Denca;CDKA;1 was clustered into the plant group and was distant from the animal and fungal groups. The modeled three-dimensional structure of Denca;CDKA;1 exhibited the similar functional structure of a fold consisting of β-sheets and α-helices joined by discontinuous random coils forming two relatively independent lobes. Quantitative real-time PCR analysis revealed that Denca;CDKA;1 transcripts were the most abundant in protocorm-like bodies with 4.76 fold, followed by that in roots (4.19 fold), seeds (2.57 fold), and stems (1.57 fold). This study characterized the novel Denca;CDKA;1 gene from D. candidum for the first time and the results will be useful for further functional determination of the gene.

scholarly journals Oxidization resistance and sorption properties of oleogels as new-generation fatty systems

2021 ◽  
pp. 89-95
Author(s):  
P.О. Nekrasov ◽  
◽  
N.A. Tkachenko ◽  
О.P. Nekrasov ◽  
О.M. Gudz ◽  
...  
Keyword(s):  
Sunflower Seed ◽  
Three Dimensional ◽  
Scientific Basis ◽  
Tocopherol Content ◽  
Sorption Properties ◽  
Dimensional Structure ◽  
Dispersed Phase ◽  
Technological Parameters ◽  
High Oleic Sunflower Oil ◽  
New Generation

Fats as complex mixtures of acylglycerols with lipid and non-lipid substances are an integral part of human nutrition. The presence of acylglycerols of trans-isomers of fatty acids causes many cardiovascular diseases and metabolic disorders. A promising approach to solving the problem of minimizing the content of these undesirable compounds in food recipes is to create a new generation of fat systems, oleogels, which are the subject of this study. High-oleic sunflower oil was used as a dispersion medium of oleogels, which allows obtaining systems with increased resistance to oxidation, as opposed to the oils of traditional kinds. Sunflower seed wax and tocopherols are chosen as a dispersed phase of these fatty systems. The choice of these components was based on their properties to create a three-dimensional structure in oleogels with specified thermomechanical characteristics. Currently, there is a lack of information on the influence of the content of the dispersed phase on the technological parameters of oleogels, namely oxidative resistance and sorption properties. The purpose of the presented work was to study these features of oleogels and establish their dependences on their composition. To solve this problem, the yield surface method is used in the work. The unknown values of the parameter vector were determined by using regression analysis algorithms. Deviation functionality was minimized by finding the appropriate combinations of the experimental series of predictors. A mathematical model was developed which allows predicting oxidative stability and sorption properties of oleogels based on the data on their composition. The suitable mass fractions of the components of the dispersed phase of oleogels have been determined as follows: tocopherol content is 0.10–0.14 wt.% and the sunflower seed wax content is 1.8–4.0 wt.%. The results obtained can serve as a scientific basis for the development of technology for the industrial production of oleogels as new generation fatty systems.

The Perseus OB2 Superbubble and the Taurus-Auriga-California-Perseus Molecular Cloud Loop

2021 ◽  
Author(s):  
Xuepeng Chen ◽  
Weihua Guo ◽  
Jiangcheng Feng ◽  
Yang Su ◽  
Yan Sun ◽  
...  
Keyword(s):  
Atomic Hydrogen ◽  
Molecular Cloud ◽  
Three Dimensional ◽  
Solar Neighborhood ◽  
Dimensional Structure ◽  
Wide Field ◽  
Star Forming ◽  
Stellar Feedback ◽  
History Of ◽  
Cloud Complex

Abstract Located at a distance of about 300 pc, Perseus OB2 (or Per~OB2 for short) is one of the major OB associations in the solar vicinity\cite{Zeeuw99,Belikov2002}, which has blown a supershell with a diameter of about 15 degree seen in the atomic hydrogen line surveys\cite{Sancisi1974,Heiles1984,Hartmann1997}. It was long considered that stellar feedback from the Per~OB2 association had formed a superbubble that swept up the surrounding interstellar medium into the observed supershell\cite{Bally2008}. Here we report the three-dimensional structure of the Per~OB2 superbubble, based on wide-field atomic hydrogen and molecular gas (traced by CO) surveys. The measured diameter of the superbubble is roughly 330 pc. Multiple atomic hydrogen shells/loops with expansion velocities of about 10 km/s are revealed in the superbubble, suggesting a complicated evolution history of the superbubble. Furthermore, the inspections of the morphology, kinematics and timescale of the Taurus-Auriga, California, and Perseus molecular clouds shows that the cloud complex is a super molecular cloud loop circling around and co-expanding with the Per~OB2 superbubble. We conclude that the Taurus-Auriga-California-Perseus loop, the largest star-forming molecular cloud complex in the solar neighborhood, is formed from the feedback of the Per~OB2 superbubble.

scholarly journals On the time variability of the HH jet ejection process

2010 ◽  
Vol 6 (S275) ◽  
pp. 392-395
Author(s):  
Fabio De Colle
Keyword(s):  
Large Scale ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Velocity Variation ◽  
Time Variability ◽  
Ejection Process ◽  
Regularization Techniques ◽  
History Of ◽  
Density Map ◽  
Electron Density Map

AbstractTwo-dimensional emission line images of the HH30 jet were recently used (De Colle et al. 2010) to recover the three-dimensional structure of the jet by applying standard tomographic technique (“Tikhonov regularization techniques”). In this paper I show that it is possible to determine the ejection history of the HH30 jet by directly comparing the outcome of numerical simulations with the results of the tomographic inversion. In particular, it is shown that the HH30 jet electron density map is best reproduced by assuming a velocity variation at the base of the jet with a large scale periodicity (with a period of ~3 yrs) added to small scales velocity variation (with periods ≲months).

Unfolding single RNA molecules: bridging the gap between equilibrium and non-equilibrium statistical thermodynamics

2005 ◽  
Vol 38 (4) ◽  
pp. 291-301 ◽  
Author(s):  
Carlos Bustamante
Keyword(s):  
Single Molecule ◽  
Molecular Motors ◽  
Biological Systems ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Fluctuation Theorems ◽  
Rna Molecules ◽  
The Times ◽  
Non Equilibrium

During the last 15 years, scientists have developed methods that permit the direct mechanical manipulation of individual molecules. Using this approach, they have begun to investigate the effect of force and torque in chemical and biochemical reactions. These studies span from the study of the mechanical properties of macromolecules, to the characterization of molecular motors, to the mechanical unfolding of individual proteins and RNA. Here I present a review of some of our most recent results using mechanical force to unfold individual molecules of RNA. These studies make it possible to follow in real time the trajectory of each molecule as it unfolds and characterize the various intermediates of the reaction. Moreover, if the process takes place reversibly it is possible to extract both kinetic and thermodynamic information from these experiments at the same time that we characterize the forces that maintain the three-dimensional structure of the molecule in solution. These studies bring us closer to the biological unfolding processes in the cell as they simulate in vitro, the mechanical unfolding of RNAs carried out in the cell by helicases. If the unfolding process occurs irreversibly, I show here that single-molecule experiments can still provide equilibrium, thermodynamic information from non-equilibrium data by using recently discovered fluctuation theorems. Such theorems represent a bridge between equilibrium and non-equilibrium statistical mechanics. In fact, first derived in 1997, the first experimental demonstration of the validity of fluctuation theorems was obtained by unfolding mechanically a single molecule of RNA. It is perhaps a sign of the times that important physical results are these days used to extract information about biological systems and that biological systems are being used to test and confirm fundamental new laws in physics.

scholarly journals Two clusters of surface-exposed amino acid residues enable high-affinity binding of retinal degeneration-3 (RD3) protein to retinal guanylyl cyclase

2020 ◽  
Vol 295 (31) ◽  
pp. 10781-10793 ◽  
Author(s):  
Igor V. Peshenko ◽  
Alexander M. Dizhoor
Keyword(s):  
Retinal Degeneration ◽  
Guanylyl Cyclase ◽  
Molecular Mechanisms ◽  
Three Dimensional ◽  
Hek293 Cells ◽  
Dimensional Structure ◽  
Amino Acid Residues ◽  
Retinal Guanylyl Cyclase ◽  
Functional Interface

Retinal degeneration-3 (RD3) protein protects photoreceptors from degeneration by preventing retinal guanylyl cyclase (RetGC) activation via calcium-sensing guanylyl cyclase–activating proteins (GCAP), and RD3 truncation causes severe congenital blindness in humans and other animals. The three-dimensional structure of RD3 has recently been established, but the molecular mechanisms of its inhibitory binding to RetGC remain unclear. Here, we report the results of probing 133 surface-exposed residues in RD3 by single substitutions and deletions to identify side chains that are critical for the inhibitory binding of RD3 to RetGC. We tested the effects of these substitutions and deletions in vitro by reconstituting purified RD3 variants with GCAP1-activated human RetGC1. Although the vast majority of the surface-exposed residues tolerated substitutions without loss of RD3's inhibitory activity, substitutions in two distinct narrow clusters located on the opposite sides of the molecule effectively suppressed RD3 binding to the cyclase. The first surface-exposed cluster included residues adjacent to Leu63 in the loop connecting helices 1 and 2. The second cluster surrounded Arg101 on a surface of helix 3. Single substitutions in those two clusters drastically, i.e. up to 245-fold, reduced the IC50 for the cyclase inhibition. Inactivation of the two binding sites completely disabled binding of RD3 to RetGC1 in living HEK293 cells. In contrast, deletion of 49 C-terminal residues did not affect the apparent affinity of RD3 for RetGC. Our findings identify the functional interface on RD3 required for its inhibitory binding to RetGC, a process essential for protecting photoreceptors from degeneration.

scholarly journals De Novo Design of a Nanopore for DNA Detection that Incorporates a β-Hairpin Peptide

2021 ◽  
Author(s):  
Keisuke Shimizu ◽  
Batsaikhan Mijiddorj ◽  
Masataka Usami ◽  
Shuhei Yoshida ◽  
Shiori Akayama ◽  
...  
Keyword(s):  
Single Molecule ◽  
Protein Design ◽  
Lipid Membrane ◽  
De Novo ◽  
Three Dimensional ◽  
Bilayer Lipid Membrane ◽  
De Novo Design ◽  
Dimensional Structure ◽  
Practical Applications ◽  
Single Molecule Level

Abstract The amino acid sequence of a protein encodes information on its three-dimensional structure and specific functionality. De novo protein design has emerged as a method to manipulate the primary structure for the development of artificial proteins and peptides with desired functionality. This paper describes the de novo design of a pore-forming peptide that has a β-hairpin structure and assembles to form a stable nanopore in a bilayer lipid membrane. This large synthetic nanopore is an entirely artificial device with practical applications. This peptide, named SV28, forms nanopore structures ranging from 1.6 to 6.2 nm in diameter assembled from 7 to 18 monomers. The nanopore formed with a diameter of 5 nm is able to detect long double-stranded DNA (dsDNA) with 1 kbp length. Moreover, the larger sized nanopore can discriminate and human telomeric DNA (G-quadruplex, G4). The blocking current signals allowed us to investigate the translocation behavior of dsDNA or G4 structure at the single molecule level. Such de novo design of peptide sequences has the potential to create novel nanopores, which would be applicable in molecular transporter between across lipid membrane.

scholarly journals Cellular Electron Cryo-Tomography to Study Virus-Host Interactions

2020 ◽  
Vol 7 (1) ◽  
pp. 239-262
Author(s):  
Emmanuelle R.J. Quemin ◽  
Emily A. Machala ◽  
Benjamin Vollmer ◽  
Vojtěch Pražák ◽  
Daven Vasishtan ◽  
...  
Keyword(s):  
Viral Entry ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Virus Assembly ◽  
Three Dimensional ◽  
Surface Proteins ◽  
Host Cells ◽  
Phase Plate ◽  
Structural Cell ◽  
Host Interactions

Viruses are obligatory intracellular parasites that reprogram host cells upon infection to produce viral progeny. Here, we review recent structural insights into virus-host interactions in bacteria, archaea, and eukaryotes unveiled by cellular electron cryo-tomography (cryoET). This advanced three-dimensional imaging technique of vitreous samples in near-native state has matured over the past two decades and proven powerful in revealing molecular mechanisms underlying viral replication. Initial studies were restricted to cell peripheries and typically focused on early infection steps, analyzing surface proteins and viral entry. Recent developments including cryo-thinning techniques, phase-plate imaging, and correlative approaches have been instrumental in also targeting rare events inside infected cells. When combined with advances in dedicated image analyses and processing methods, details of virus assembly and egress at (sub)nanometer resolution were uncovered. Altogether, we provide a historical and technical perspective and discuss future directions and impacts of cryoET for integrative structural cell biology analyses of viruses.

De Novo Design of a Nanopore for DNA Detection Incorporating a β-hairpin Peptide

2020 ◽  
Author(s):  
Keisuke Shimizu ◽  
Batsaikhan Mijiddorj ◽  
Shuhei Yoshida ◽  
Shiori Akayama ◽  
Yoshio Hamada ◽  
...  
Keyword(s):  
Single Molecule ◽  
Protein Design ◽  
Lipid Membrane ◽  
De Novo ◽  
Three Dimensional ◽  
Bilayer Lipid Membrane ◽  
De Novo Design ◽  
Dimensional Structure ◽  
Practical Applications ◽  
Single Molecule Level

The amino acid sequence of a protein encodes information on its three-dimensional structure and specific functionality. De novo protein design has emerged as a method to manipulate the primary structure for the development of artificial proteins and peptides with desired functionality. This paper describes the de novo design of a pore-forming peptide that has a β-hairpin structure and assembles to form a stable nanopore in a bilayer lipid membrane. This large synthetic nanopore is an entirely artificial device with practical applications. This peptide, named SV28, forms nanopore structures ranging from 1.6 to 6.2 nm in diameter assembled from 7 to 18 monomers. The nanopore formed with a diameter of 5 nm is able to detect long double-stranded DNA (dsDNA) with 1 kbp length, and measurement of current signals allowed us to investigate the translocation behavior of dsDNA at the single molecule level. Such de novo design of peptide sequences has the potential to create assembled structure in lipid membrane such as novel nanopores, which would also be applicable in molecular transporter between inside and outside of lipid membrane.

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