scholarly journals An allosteric Sec61 inhibitor traps nascent transmembrane helices at the lateral gate

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Andrew L MacKinnon ◽  
Ville O Paavilainen ◽  
Ajay Sharma ◽  
Ramanujan S Hegde ◽  
Jack Taunton
Keyword(s):  
Genetic Selection ◽  
Transmembrane Helices ◽  
Biophysical Properties ◽  
Site Specific ◽  
Protein Biogenesis ◽  
Site Of Action ◽  
Lateral Gate ◽  
Insight Into ◽  
Sec61 Channel ◽  
Selection Of

Membrane protein biogenesis requires the coordinated movement of hydrophobic transmembrane domains (TMD) from the cytosolic vestibule of the Sec61 channel into the lipid bilayer. Molecular insight into TMD integration has been hampered by the difficulty of characterizing intermediates during this intrinsically dynamic process. In this study, we show that cotransin, a substrate-selective Sec61 inhibitor, traps nascent TMDs in the cytosolic vestibule, permitting detailed interrogation of an early pre-integration intermediate. Site-specific crosslinking revealed the pre-integrated TMD docked to Sec61 near the cytosolic tip of the lateral gate. Escape from cotransin-arrest depends not only on cotransin concentration, but also on the biophysical properties of the TMD. Genetic selection of cotransin-resistant cancer cells uncovered multiple mutations clustered near the lumenal plug of Sec61α, thus revealing cotransin’s likely site of action. Our results suggest that TMD/lateral gate interactions facilitate TMD transfer into the membrane, a process that is allosterically modulated by cotransin binding to the plug.

scholarly journals A unified evolutionary origin for SecY and YidC

2020 ◽  
Author(s):  
Aaron J. O. Lewis ◽  
Ramanujan S. Hegde
Keyword(s):  
Membrane Protein ◽  
Family Members ◽  
Evolutionary Origin ◽  
Transmembrane Helices ◽  
Conducting Channel ◽  
Helix Bundle ◽  
Protein Biogenesis ◽  
Lateral Gate

AbstractCells use transporters to move protein across membranes, but the most ancient transporters’ origins are unknown. Here, we analyse the protein-conducting channel SecY and deduce a plausible path to its evolution. We find that each of its pseudosymmetric halves consists of a three-helix bundle interrupted by a two-helix hairpin. Unexpectedly, we identify this same motif in the YidC family of membrane protein biogenesis factors, which is similarly ancient as SecY. In YidC, the two-helix hairpin faces the cytosol and facilitates substrate delivery, whereas in SecY it forms the substratebinding transmembrane helices of the lateral gate. We propose that SecY originated as a YidC homolog which formed a channel by juxtaposing two hydrophilic grooves in an antiparallel homodimer. Archaeal and eukaryotic YidC family members have repurposed this interface to heterodimerise with conserved partners. Unification of the two ancient membrane protein biogenesis factors reconstructs a key step in the evolution of cells.

scholarly journals Stepwise gating of the Sec61 protein-conducting channel by Sec63 and Sec62

2020 ◽  
Author(s):  
Samuel Itskanov ◽  
Eunyong Park
Keyword(s):  
Electron Microscopy ◽  
Transmembrane Helices ◽  
Conducting Channel ◽  
Essential Step ◽  
Gating Mechanisms ◽  
Cryo Electron Microscopy ◽  
Gate Opening ◽  
Lateral Gate ◽  
Sec61 Channel ◽  
Hierarchical Manner

SummaryThe universally conserved Sec61/SecY channel mediates transport of many newly synthesized polypeptides across membranes, an essential step in protein secretion and membrane protein integration1-5. The channel has two gating mechanisms—a lipid-facing lateral gate, through which hydrophobic signal sequences or transmembrane helices (TMs) are released into the membrane, and a vertical gate, called the plug, which regulates the water-filled pore required for translocation of hydrophilic polypeptide segments6. Currently, how these gates are controlled and how they regulate the translocation process remain poorly understood. Here, by analyzing cryo-electron microscopy (cryo-EM) structures of several variants of the eukaryotic post-translational translocation complex Sec61-Sec62-Sec63, we reveal discrete gating steps of Sec61 and the mechanism by which Sec62 and Sec63 induce these gating events. We show that Sec62 forms a V-shaped structure in front of the lateral gate to fully open both gates of Sec61. Without Sec62, the lateral gate opening narrows, and the vertical pore becomes closed by the plug, rendering the channel inactive. We further show that the lateral gate is opened first by interactions between Sec61 and Sec63 in both cytosolic and luminal domains, a simultaneous disruption of which fully closes the channel. Our study defines the function of Sec62 and illuminates how Sec63 and Sec62 work together in a hierarchical manner to activate the Sec61 channel for post-translational translocation.

An Insight into Oligopeptide Transporter 3 (OPT3) family proteins

2020 ◽  
Vol 27 ◽  
Author(s):  
Fırat Kurt
Keyword(s):  
Stress Responses ◽  
Chelating Agent ◽  
Biological Processes ◽  
Biotic And Abiotic Stress ◽  
Oligopeptide Transporter ◽  
Binding Residues ◽  
Fe Homeostasis ◽  
Proteins Interactions ◽  
Insight Into ◽  
Selection Of

: Oligopeptide transporter 3 (OPT3) proteins are one of the subsets of OPT clade, yet little is known about these transporters. Therefore, homolog OPT3 proteins in several plant species were investigated and characterized using bioinformatical tools. Motif and co-expression analyses showed that OPT3 proteins may be involved in both biotic and abiotic stress responses as well as growth and developmental processes. AtOPT3 usually seemed to take part in Fe homeostasis whereas ZmOPT3 putatively interacted with proteins involved in various biological processes from plant defense system to stress responses. Glutathione (GSH), as a putative alternative chelating agent, was used in the AtOPT3 and ZmOPT3 docking analyses to identify their putative binding residues. The information given in this study will contribute to the understanding of OPT3 proteins’ interactions in various pathways and to the selection of potential ligands for OPT3s.

scholarly journals Prediction of meat quality traits in the abattoir using portable near-infrared spectrometers: heritability of predicted traits and genetic correlations with laboratory-measured traits

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Simone Savoia ◽  
Andrea Albera ◽  
Alberto Brugiapaglia ◽  
Liliana Di Stasio ◽  
Alessio Cecchinato ◽  
...  
Keyword(s):  
Meat Quality ◽  
Near Infrared ◽  
External Validation ◽  
Genetic Correlations ◽  
Genetic Selection ◽  
Quality Traits ◽  
Eye Muscle ◽  
Meat Quality Traits ◽  
Color Traits ◽  
Selection Of

Abstract Background The possibility of assessing meat quality traits over the meat chain is strongly limited, especially in the context of selective breeding which requires a large number of phenotypes. The main objective of this study was to investigate the suitability of portable infrared spectrometers for phenotyping beef cattle aiming to genetically improving the quality of their meat. Meat quality traits (pH, color, water holding capacity, tenderness) were appraised on rib eye muscle samples of 1,327 Piemontese young bulls using traditional (i.e., reference/gold standard) laboratory analyses; the same traits were also predicted from spectra acquired at the abattoir on the intact muscle surface of the same animals 1 d after slaughtering. Genetic parameters were estimated for both laboratory measures of meat quality traits and their spectra-based predictions. Results The prediction performances of the calibration equations, assessed through external validation, were satisfactory for color traits (R2 from 0.52 to 0.80), low for pH and purge losses (R2 around 0.30), and very poor for cooking losses and tenderness (R2 below 0.20). Except for lightness and purge losses, the heritability estimates of most of the predicted traits were lower than those of the measured traits while the genetic correlations between measured and predicted traits were high (average value 0.81). Conclusions Results showed that NIRS predictions of color traits, pH, and purge losses could be used as indicator traits for the indirect genetic selection of the reference quality phenotypes. Results for cooking losses were less effective, while the NIR predictions of tenderness were affected by a relatively high uncertainty of estimate. Overall, genetic selection of some meat quality traits, whose direct phenotyping is difficult, can benefit of the application of infrared spectrometers technology.

Exact analysis of the bending of wide beams by a modified elastica approach

2011 ◽  
Vol 225 (11) ◽  
pp. 2759-2764 ◽  
Author(s):  
L F Campanile ◽  
R Jähne ◽  
A Hasse
Keyword(s):  
Finite Element ◽  
Substantial Reduction ◽  
Short Review ◽  
Computational Effort ◽  
Two Dimensional ◽  
Finite Element Calculations ◽  
Dimensional Finite Element ◽  
Wide Beams ◽  
Insight Into ◽  
Selection Of

Classical beam models do not account for partial restraint of anticlastic bending and are therefore inherently inaccurate. This article proposes a modification of the exact Bernoulli–Euler equation which allows for an exact prediction of the beam's deflection without the need of two-dimensional finite element calculations. This approach offers a substantial reduction in the computational effort, especially when coupled with a fast-solving schema like the circle-arc method. Besides the description of the new method and its validation, this article offers an insight into the somewhat disregarded topic of anticlastic bending by a short review of the published theories and a selection of representative numerical results.

Design and topological optimization of rear pressure bulkhead for a typical aircraft

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Marshal Thakran ◽  
Meenakshi ◽  
Jitender Sharma ◽  
Charles Gilbert Martin
Keyword(s):  
Numerical Analysis ◽  
Significant Influence ◽  
Design Methodology ◽  
Structural Integrity ◽  
Topological Optimization ◽  
Content Type ◽  
Iterative Design ◽  
Practical Implications ◽  
Insight Into ◽  
Selection Of

Purpose The purpose of this paper is to evaluate the model of a rear pressure bulkhead with different design optimizations to meet the pressurized cabin requirements of an aircraft. Design/methodology/approach This paper presents the results of the static analysis of a dome-shaped rear pressure bulkhead model designed in Catia-v5. Numerical analysis of model meshed in hyper-mesh and solved using Opti-Struct for iterative design optimizations. Findings All the iterative models are analyzed at 9 Psi. Rear pressure bulkhead designed with L-section stringer shows better results than the model optimized with T-section stringer for the same thickness. The model optimized with L-shaped stinger also reduces the weight of the bulkhead without affecting the structural integrity. Practical implications It has been concluded in this paper that the selection of specific shapes of the stringers shows a significant influence on weight reduction. Originality/value This paper provides a topical, technical insight into the design and development of a rear pressure bulkhead. It also outlines the future development of dome-shaped rear pressure bulkhead.

Paradata in Documentation Standards and Recommendations for Digital Archaeological Visualisations

2020 ◽  
Vol 6 (2) ◽  
pp. 191-220
Author(s):  
Lisa Börjesson ◽  
Olle Sköld ◽  
Isto Huvila
Keyword(s):  
Research Data ◽  
Data Reuse ◽  
Lack Of Information ◽  
National Heritage ◽  
Processing History ◽  
International Harmonisation ◽  
Insight Into ◽  
Current Standards ◽  
Selection Of ◽  
As If

Abstract Digitalisation of research data and massive efforts to make it findable, accessible, interoperable, and reusable has revealed that in addition to an eventual lack of description of the data itself (metadata), data reuse is often obstructed by the lack of information about the datamaking and interpretation (i.e. paradata). In search of the extent and composition of categories for describing processes, this article reviews a selection of standards and recommendations frequently referred to as useful for documenting archaeological visualisations. It provides insight into 1) how current standards can be employed to document provenance and processing history (i.e. paradata), and 2) what aspects of the processing history can be made transparent using current standards and which aspects are pushed back or hidden. The findings show that processes are often either completely absent or only partially addressed in the standards. However, instead of criticising standards for bias and omissions as if a perfect description of everything would be attainable, the findings point to the need for a comprehensive consideration of the space a standard is operating in (e.g. national heritage administration or international harmonisation of data). When a standard is used in a specific space it makes particular processes, methods, or tools transparent. Given these premises, if the standard helps to document what needs to be documented (e.g. paradata), and if it provides a type of transparency required in a certain space, it is reasonable to deem the standard good enough for that purpose.

Prescreening in large populations as a tool for identifying elevated CO2-responsive genotypes in plants

2019 ◽  
Vol 46 (1) ◽  
pp. 1 ◽  
Author(s):  
Hiroyuki Shimono ◽  
Graham Farquhar ◽  
Matthew Brookhouse ◽  
Florian A. Busch ◽  
Anthony O'Grady ◽  
...  
Keyword(s):  
Genetic Selection ◽  
Co2 Concentration ◽  
Elevated Atmospheric Co2 ◽  
High Performing ◽  
Active Selection ◽  
Wide Range ◽  
Large Populations ◽  
Increase Productivity ◽  
The Cost ◽  
Selection Of

Elevated atmospheric CO2 concentration (e[CO2]) can stimulate the photosynthesis and productivity of C3 species including food and forest crops. Intraspecific variation in responsiveness to e[CO2] can be exploited to increase productivity under e[CO2]. However, active selection of genotypes to increase productivity under e[CO2] is rarely performed across a wide range of germplasm, because of constraints of space and the cost of CO2 fumigation facilities. If we are to capitalise on recent advances in whole genome sequencing, approaches are required to help overcome these issues of space and cost. Here, we discuss the advantage of applying prescreening as a tool in large genome×e[CO2] experiments, where a surrogate for e[CO2] was used to select cultivars for more detailed analysis under e[CO2] conditions. We discuss why phenotypic prescreening in population-wide screening for e[CO2] responsiveness is necessary, what approaches could be used for prescreening for e[CO2] responsiveness, and how the data can be used to improve genetic selection of high-performing cultivars. We do this within the framework of understanding the strengths and limitations of genotype–phenotype mapping.

scholarly journals Biological control of tick populations: review and reflections

1994 ◽  
Vol 10 (1) ◽  
pp. 47-52 ◽  
Author(s):  
Norma V. Labarthe
Keyword(s):  
Biological Control ◽  
Genetic Selection ◽  
Effective Vaccine ◽  
Control Methods ◽  
The Relationship ◽  
Selection Of

This study is concerned with aspects of the relationship between ticks and their hosts that have a bearing on biological control of tick populations. It proposes control methods based on a program that would combine development of an effective vaccine with genetic selection of hosts.

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