scholarly journals Ribosome exit tunnel electrostatics

2020 ◽  
Author(s):  
Marc Joiret ◽  
Francesca Rapino ◽  
Pierre Close ◽  
Liesbet Geris
Keyword(s):  
Translational Control ◽  
Elongation Rate ◽  
Electrostatic Model ◽  
Amino Acid Residues ◽  
Physical Description ◽  
Axial Forces ◽  
Entry Points ◽  
Exit Tunnel ◽  
Ribosome Exit Tunnel ◽  
The Impact

AbstractThe impact of the ribosome exit tunnel electrostatics on the protein elongation rate or on the forces acting upon the nascent polypeptide chain are currently not fully elucidated. In the past, researchers have measured the electrostatic potential inside the ribosome polypeptide exit tunnel at a limited number of spatial points, at least in prokaryotes. Here, we present a basic electrostatic model of the exit tunnel of the ribosome, providing a quantitative physical description of the tunnel interaction with the nascent proteins at all centro-axial points inside the tunnel. We show how the tunnel geometry causes a positive potential difference between the tunnel exit and entry points which impedes positively charged amino acid residues from progressing through the tunnel, affecting the elongation rate in a range of minus 40% to plus 85% when compared to the average elongation rate. The time spent by the ribosome to decode the genetic encrypted message is constrained accordingly. We quantitatively derived, at single residue resolution, the axial forces acting on the nascent peptide from its particular sequence embedded in the tunnel. The model sheds light on how the experimental data point measurements of the potential are linked to the local structural chemistry of the inner wall and the shape and size of the tunnel. The model consistently connects experimental observations coming from different fields in molecular biology, structural and physical chemistry, biomechanics, synthetic and multi-omics biology. Our model should be a valuable tool to gain insight into protein synthesis dynamics, translational control and into the role of the ribosome’s mechanochemistry in the co-translational protein folding.

scholarly journals The impact of ribosomal interference, codon usage, and exit tunnel interactions on translation elongation rate variation

2016 ◽  
Author(s):  
Khanh Dao Duc ◽  
Yun S. Song
Keyword(s):  
Electrostatic Interactions ◽  
Elongation Rate ◽  
Ribosome Profiling ◽  
Rate Variation ◽  
Biophysical Properties ◽  
Translation Elongation ◽  
Nascent Polypeptide ◽  
Exit Tunnel ◽  
Pass Through ◽  
The Impact

ABSTRACTPrevious studies have shown that translation elongation is regulated by multiple factors, but the observed heterogeneity remains only partially explained. To dissect quantitatively the different determinants of elongation speed, we use probabilistic modeling to estimate initiation and local elongation rates from ribosome profiling data. This model-based approach allows us to quantify the extent of interference between ribosomes on the same transcript. We show that neither interference nor the distribution of slow codons is sufficient to explain the observed heterogeneity. Instead, we find that electrostatic interactions between the ribosomal exit tunnel and specific parts of the nascent polypeptide govern the elongation rate variation as the polypeptide makes its initial pass through the tunnel. Once the N-terminus has escaped the tunnel, the hydropathy of the nascent polypeptide within the ribosome plays a major role in modulating the speed. We show that our results are consistent with the biophysical properties of the tunnel.

Influence of nascent polypeptide positive charges on translation dynamics

2020 ◽  
Vol 477 (15) ◽  
pp. 2921-2934
Author(s):  
Rodrigo D. Requião ◽  
Géssica C. Barros ◽  
Tatiana Domitrovic ◽  
Fernando L. Palhano
Keyword(s):  
Mrna Decay ◽  
Translation Termination ◽  
Published Data ◽  
Translation Efficiency ◽  
Amino Acid Residues ◽  
High Concentration ◽  
Strong Argument ◽  
Translation Arrest ◽  
Exit Tunnel ◽  
Positively Charged

Protein segments with a high concentration of positively charged amino acid residues are often used in reporter constructs designed to activate ribosomal mRNA/protein decay pathways, such as those involving nonstop mRNA decay (NSD), no-go mRNA decay (NGD) and the ribosome quality control (RQC) complex. It has been proposed that the electrostatic interaction of the positively charged nascent peptide with the negatively charged ribosomal exit tunnel leads to translation arrest. When stalled long enough, the translation process is terminated with the degradation of the transcript and an incomplete protein. Although early experiments made a strong argument for this mechanism, other features associated with positively charged reporters, such as codon bias and mRNA and protein structure, have emerged as potent inducers of ribosome stalling. We carefully reviewed the published data on the protein and mRNA expression of artificial constructs with diverse compositions as assessed in different organisms. We concluded that, although polybasic sequences generally lead to lower translation efficiency, it appears that an aggravating factor, such as a nonoptimal codon composition, is necessary to cause translation termination events.

Working at the Crossroads: A Guide for Border Crossing

2017 ◽  
Vol 4 (2) ◽  
Author(s):  
John Mckiernan-González
Keyword(s):  
American Studies ◽  
Collaborative Work ◽  
Border Crossing ◽  
Keynote Address ◽  
Cross Border ◽  
Entry Points ◽  
Academic Labor ◽  
Boyle Heights ◽  
The University ◽  
The Impact

This article discusses the impact of George J. Sánchez’s keynote address “Working at the Crossroads” in making collaborative cross-border projects more academically legitimate in American studies and associated disciplines. The keynote and his ongoing administrative labor model the power of public collaborative work to shift research narratives. “Working at the Crossroads” demonstrated how historians can be involved—as historians—in a variety of social movements, and pointed to the ways these interactions can, and maybe should, shape research trajectories. It provided a key blueprint and key examples for doing historically informed Latina/o studies scholarship with people working outside the university. Judging by the success of Sánchez’s work with Boyle Heights and East LA, projects need to establish multiple entry points, reward participants at all levels, and connect people across generations.I then discuss how I sought to emulate George Sánchez’s proposals in my own work through partnering with labor organizations, developing biographical public art projects with students, and archiving social and cultural histories. His keynote address made a back-and-forth movement between home communities and academic labor seem easy and professionally rewarding as well as politically necessary, especially in public universities. 

scholarly journals Driven Pile Effects on Nearby Cylindrical and Semi-Tapered Pile in Sandy Clay

2021 ◽  
Vol 11 (7) ◽  
pp. 2919
Author(s):  
Massamba Fall ◽  
Zhengguo Gao ◽  
Becaye Cissokho Ndiaye
Keyword(s):  
Coupling Effect ◽  
Lateral Displacement ◽  
Bending Moment ◽  
Adaptive Mesh ◽  
Pile Driving ◽  
Arbitrary Lagrangian Eulerian ◽  
Axial Forces ◽  
Tapered Pile ◽  
Driven Pile ◽  
The Impact

A pile foundation is commonly adopted for transferring superstructure loads into the ground in weaker soil. They diminish the settlement of the infrastructure and augment the soil-bearing capacity. This paper emphases the pile-driving effect on an existing adjacent cylindrical and semi-tapered pile. Driving a three-dimensional pile into the ground is fruitfully accomplished by combining the arbitrary Lagrangian–Eulerian (ALE) adaptive mesh and element deletion methods without adopting any assumptions that would simplify the simulation. Axial forces, bending moment, and lateral displacement were studied in the neighboring already-installed pile. An investigation was made into some factors affecting the forces and bending moment, such as pile spacing and the shape of the already-installed pile (cylindrical, tapered, or semi-tapered). An important response was observed in the impact of the driven pile on the nearby existing one, the bending moment and axial forces were not negligible, and when the pile was loaded, it was recommended to consider the coupling effect. Moreover, the adjacent semi-tapered pile was subjected to less axial and lateral movement than the cylindrical one with the same length and volume for taper angles smaller than 1.0°, and vice versa for taper angles greater than 1.4°.

Rubber specialization vs crop diversification: the roles of perceived risks

2017 ◽  
Vol 9 (2) ◽  
pp. 188-210 ◽  
Author(s):  
Shi Min ◽  
Jikun Huang ◽  
Hermann Waibel
Keyword(s):  
Land Use ◽  
Land Tenure ◽  
Risk Perceptions ◽  
Household Wealth ◽  
Environmental Conservation ◽  
Crop Diversification ◽  
Cross Sectional Survey ◽  
Content Type ◽  
Entry Points ◽  
The Impact

Purpose The purpose of this paper is to examine the impact of farmers’ risk perceptions regarding rubber farming on their land use choices, including rubber specialization and crop diversification. Design/methodology/approach A cross-sectional survey data of some 600 smallholder rubber farmers in Xishuangbanna in Southwest China is employed. This paper develops a general conceptual framework that incorporates a subjective risk item into a model of farmers’ land use choices, thereby developing four econometric models to estimate the role of risk perceptions, and applies instrumental variables to control for the endogeneity of risk perceptions. Findings The results demonstrate that risk perceptions play an important role in smallholders’ decision-making regarding land use strategies to address potential risks in rubber farming. Smallholders with higher risk perceptions specialize in rubber farming less often and are more likely to diversify their land use, thereby contributing to local environmental conservation in terms of agrobiodiversity. The land use choices of smallholder rubber farmers are also associated with ethnicity, household wealth, off-farm employment, land tenure status, altitude and rubber farming experience. Originality/value This study contributes to a better understanding of the implications of farmers’ risk perceptions and shows entry points for improving the sustainability of rubber-based land use systems.

scholarly journals Novel antibody binding determinants on the capsid surface of serotype O foot-and-mouth disease virus

2014 ◽  
Vol 95 (5) ◽  
pp. 1104-1116 ◽  
Author(s):  
Amin S. Asfor ◽  
Sasmita Upadhyaya ◽  
Nick J. Knowles ◽  
Donald P. King ◽  
David J. Paton ◽  
...  
Keyword(s):  
Amino Acid ◽  
Guinea Pig ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Amino Acid Residues ◽  
Serotype O ◽  
Antigenic Sites ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
The Impact

Five neutralizing antigenic sites have been described for serotype O foot-and-mouth disease viruses (FMDV) based on monoclonal antibody (mAb) escape mutant studies. However, a mutant virus selected to escape neutralization of mAb binding at all five sites was previously shown to confer complete cross-protection with the parental virus in guinea pig challenge studies, suggesting that amino acid residues outside the mAb binding sites contribute to antibody-mediated in vivo neutralization of FMDV. Comparison of the ability of bovine antisera to neutralize a panel of serotype O FMDV identified three novel putative sites at VP2-74, VP2-191 and VP3-85, where amino acid substitutions correlated with changes in sero-reactivity. The impact of these positions was tested using site-directed mutagenesis to effect substitutions at critical amino acid residues within an infectious copy of FMDV O1 Kaufbeuren (O1K). Recovered viruses containing additional mutations at VP2-74 and VP2-191 exhibited greater resistance to neutralization with both O1K guinea pig and O BFS bovine antisera than a virus that was engineered to include only mutations at the five known antigenic sites. The changes at VP2-74 and VP3-85 are adjacent to critical amino acids that define antigenic sites 2 and 4, respectively. However VP2-191 (17 Å away from VP2-72), located at the threefold axis and more distant from previously identified antigenic sites, exhibited the most profound effect. These findings extend our knowledge of the surface features of the FMDV capsid known to elicit neutralizing antibodies, and will improve our strategies for vaccine strain selection and rational vaccine design.

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