scholarly journals Structure and mechanisms of sodium-pumping KR2 rhodopsin

2019 ◽  
Vol 5 (4) ◽  
pp. eaav2671 ◽  
Author(s):  
Kirill Kovalev ◽  
Vitaly Polovinkin ◽  
Ivan Gushchin ◽  
Alexey Alekseev ◽  
Vitaly Shevchenko ◽  
...  
Keyword(s):  
Proton Pump ◽  
Functional Data ◽  
Rational Design ◽  
Biological Function ◽  
Low Ph ◽  
Biotechnological Applications ◽  
Atomic Structures ◽  
Existing Structures ◽  
Sodium Pumping ◽  
Microbial Rhodopsin

Rhodopsins are the most universal biological light-energy transducers and abundant phototrophic mechanisms that evolved on Earth and have a remarkable diversity and potential for biotechnological applications. Recently, the first sodium-pumping rhodopsin KR2 fromKrokinobacter eikastuswas discovered and characterized. However, the existing structures of KR2 are contradictory, and the mechanism of Na+pumping is not yet understood. Here, we present a structure of the cationic (non H+) light-driven pump at physiological pH in its pentameric form. We also present 13 atomic structures and functional data on the KR2 and its mutants, including potassium pumps, which show that oligomerization of the microbial rhodopsin is obligatory for its biological function. The studies reveal the structure of KR2 at nonphysiological low pH where it acts as a proton pump. The structure provides new insights into the mechanisms of microbial rhodopsins and opens the way to a rational design of novel cation pumps for optogenetics.

Improving catalytic efficiency and maximum activity at low pH of Aspergillus neoniger phytase using rational design

2019 ◽  
Vol 131 ◽  
pp. 1117-1124 ◽  
Author(s):  
Sijia Zhou ◽  
Zhemin Liu ◽  
Wancui Xie ◽  
Yuan Yu ◽  
Chen Ning ◽  
...  
Keyword(s):  
Rational Design ◽  
Catalytic Efficiency ◽  
Maximum Activity ◽  
Low Ph

scholarly journals Poly(2-alkylacrylic acid) polymers deliver molecules to the cytosol by pH-sensitive disruption of endosomal vesicles

2003 ◽  
Vol 372 (1) ◽  
pp. 65-75 ◽  
Author(s):  
Rachel A. JONES ◽  
Charles Y. CHEUNG ◽  
Fiona E. BLACK ◽  
Jasmine K. ZIA ◽  
Patrick S. STAYTON ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Cell ◽  
Rational Design ◽  
Gene Transfection ◽  
Low Ph ◽  
Haemolytic Activity ◽  
Permeability Barrier ◽  
Cultured Human Cells ◽  
Dna Complex ◽  
Endosomal Vesicles

The permeability barrier posed by cell membranes represents a challenge for the delivery of hydrophilic molecules into cells. We previously proposed that poly(2-alkylacrylic acid)s are endocytosed by cells into acidified vesicles and are there triggered by low pH to disrupt membranes and release the contents of endosomes/lysosomes to the cytosol. If this hypothesis is correct, these polymers could be valuable in drug-delivery applications. The present paper reports functional comparisons of a family of three poly(2-alkylacrylic acid)s. Poly(2-propylacrylic acid) (PPAA), poly(2-ethylacrylic acid) (PEAA) and poly(2-methylacrylic acid) (PMAA) were compared in red-blood-cell haemolysis assays and in a lipoplex (liposome–DNA complex) assay. We also directly examined the ability of these polymers to disrupt endosomes and lysosomes in cultured human cells. Our results show that: (i) unlike membrane-disruptive peptides, the endosomal-disruptive ability of poly(2-alkylacrylic acid)s cannot necessarily be predicted from their haemolytic activity at low pH, (ii) PPAA (but not PEAA or PMAA) potently facilitates gene transfection by cationic lipoplexes and (iii) endocytosed poly(2-alkylacrylic acid)s are triggered by luminal acidification to selectively disrupt endosomes (not lysosomes) and release their contents to the cytosol. These results will facilitate the rational design of future endosomal-disrupting polymers for drug delivery.

scholarly journals Modulating the Biological Function of Protein by Tailoring the Adsorption Orientation on Nanoparticles

2020 ◽  
Author(s):  
Akhil Jain ◽  
Gustavo Trindade ◽  
Jacqueline M. Hicks ◽  
Jordan C. Pott ◽  
Ruman Rahman ◽  
...  
Keyword(s):  
Rational Design ◽  
Secondary Ion Mass Spectrometry ◽  
Biological Function ◽  
Protein Orientation ◽  
Protein Conjugates ◽  
Tof Sims ◽  
Cyt C ◽  
Apoptotic Activity ◽  
Secondary Ion

<div><div><div><p>Protein orientation in nanoparticle-protein conjugates plays a crucial role in binding to cell receptors and ultimately, defines their targeting efficiency. Therefore, understanding fundamental aspects of the role of protein orientation upon adsorption on the surface of nanoparticles (NPs) is vital for the development of clinically important protein-based nanomedicine. In this work, new insights on the effect of the different orientation of cytochrome c (cyt c) bound to gold nanoparticles (GNPs) using various ligands on its apoptotic activity is reported. Time-of-Flight Secondary-Ion Mass Spectrometry (ToF- SIMS), electrochemical and circular dichroism (CD) analyses are used to investigate the characteristics of cyt c orientation and structure on functionalized GNPs. These studies indicate that the orientation and position of the heme ring inside the cyt c structure can be altered by changing the surface chemistry on the NPs. A difference in the apoptosis inducing capability because of different orientation of cyt c bound to the GNPs is observed. These findings indicate that the biological activity of a protein can be modulated on the surface of NPs by varying its adsorption orientation. This study will impact on the rational design of new nanoscale biosensors, bioelectronics, and nanoparticle-protein based drugs.</p></div></div></div>

scholarly journals APPLICATION OF STEPWISE AND ITERATIVE METHOD IN THE CALCULATION OF BENDING PRESTRESSED PRECAST AND MONOLITHIC ELEMENTS TAKING INTO ACCOUNT PHYSICAL NONLINEARITY

2020 ◽  
pp. 12-27
Author(s):  
Polina Davidenko ◽  
Yasser Garib Sami ◽  
Andrey Shevchenko
Keyword(s):  
Reinforced Concrete ◽  
Iterative Method ◽  
Cross Section ◽  
Rational Design ◽  
Variational Principles ◽  
Structural Mechanics ◽  
Physical Nonlinearity ◽  
Method Of Calculation ◽  
Existing Structures ◽  
The Cross

precast and monolithic reinforced concrete structures with and without prestressing armature voltages are used as newly designed independent ones, and are the result of work to strengthen existing structures by increasing the cross section. In both cases, the cross-section of such elements is considered as a two-layer, and the resulting composite element operates under load in conditions distributed between the layers of internal forces, the mechanism and the actual value of the distribution of which depends on the physical and mechanical characteristics, the design scheme and the parameters of the contact interaction of the layers. When calculating and designing prestressed reinforced concrete precast and monolithic elements, the shear seam compliance is usually not taken into account, which complicates the analysis of the actual stress-strain state of the structure and contains a certain undisclosed potential for its rational design. One of the possible directions in solving the problem, taking into account the shift of the contact seam, is the use of variational principles of structural mechanics in the calculation of structures such as composite cross-section rods. In the framework of this work, the questions of practical applicability in the structural analysis of composite reinforced concrete precast-monolithic rod of variation principles of structural mechanics based on the method of V.Z. Vlasov – I.E. Mileykovsky in the form of displacements in combination with the stepwise-iterative method of calculation are considered. The results of numerical calculations by the proposed method are presented, which allows to take into account the specifics of the shear bonds of the precast and monolithic layer, to carry out practical accounting of the seam compliance, as well as to take into account the physical nonlinearity of the characteristics of materials, which allows the rational design of precast monolithic structures.

Thermophilic Bacterial Exopolysaccharides

2022 ◽  
pp. 334-361
Author(s):  
Rakesh Goswami ◽  
Bidyut Bandyopadhyay ◽  
Sanjoy Sadhukhan
Keyword(s):  
Hydrothermal Vents ◽  
Extracellular Polymeric Substances ◽  
Hot Spring ◽  
Carbon Sources ◽  
Extreme Environments ◽  
Value Added ◽  
Low Ph ◽  
Extreme Conditions ◽  
Biotechnological Applications ◽  
Bacterial Exopolysaccharides

Bacterial exopolysaccharides have enormous diversity with valuable characteristics, synthesized by various pathways in extreme conditions like salinity, geothermal springs, or hydrothermal vents. Due to extreme environments, these microorganisms have various adaption principles (e.g., low pH, high temperature, high saltation, and high radiation). Exopolysaccharide is an organic compound produced by most bacteria during fermentation using various carbon sources, resulting in a jelly-like or mass network structure outside the cell wall. This biopolymer has an adherent cohesive layer throughout the cell layer. Hot spring bacterial polysaccharides contain diverse extracellular polymeric substances. With a gain in popularity in applications of thermophilic microbial polysaccharides and its demand in diverse value-added industrial products, this chapter aims to provide valuable information on the physicochemical function and biotechnological applications in the field of food, medical imaging, nano-drugs, bioremediation, cancer, anti-bacterial, tissue engineering, etc.

scholarly journals In-depth analysis of subclass-specific conformational preferences of IgG antibodies

IUCrJ ◽  
2015 ◽  
Vol 2 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Xinsheng Tian ◽  
Bente Vestergaard ◽  
Matthias Thorolfsson ◽  
Zhiru Yang ◽  
Hanne B. Rasmussen ◽  
...  
Keyword(s):  
Small Angle ◽  
Rational Design ◽  
Biological Function ◽  
Scattering Data ◽  
Variable Regions ◽  
X Ray ◽  
X Ray Scattering ◽  
Conformational Preferences ◽  
Depth Analysis ◽  
Ray Scattering

IgG subclass-specific differences in biological function andin vitrostability are often referred to variations in the conformational flexibility, while this flexibility has rarely been characterized. Here, small-angle X-ray scattering data from IgG1, IgG2 and IgG4 antibodies, which were designed with identical variable regions, were thoroughly analysed by the ensemble optimization method. The extended analysis of the optimized ensembles through shape clustering reveals distinct subclass-specific conformational preferences, which provide new insights for understanding the variations in physical/chemical stability and biological function of therapeutic antibodies. Importantly, the way that specific differences in the linker region correlate with the solution structure of intact antibodies is revealed, thereby visualizing future potential for the rational design of antibodies with designated physicochemical properties and tailored effector functions. In addition, this advanced computational approach is applicable to other flexible multi-domain systems and extends the potential for investigating flexibility in solutions of macromolecules by small-angle X-ray scattering.

scholarly journals β11-12 linker isomerization governs Acid-sensing ion channel desensitization and recovery

2019 ◽  
Author(s):  
Matthew Rook ◽  
Abby Williamson ◽  
John D. Lueck ◽  
Maria Musgaard ◽  
David M. MacLean
Keyword(s):  
Functional Data ◽  
Resting State ◽  
Low Ph ◽  
Cross Linking ◽  
State Dependent ◽  
Acid Sensing Ion Channels ◽  
Canonical Amino Acid ◽  
Functional States ◽  
Dynamics Simulations ◽  
Fast Perfusion

AbstractAcid-sensing ion channels (ASICs) are neuronal sodium-selective channels activated by reductions in extracellular pH. Structures of the three presumptive functional states, high-pH resting, low-pH desensitized, and toxin-stabilized open, have all been solved for chicken ASIC1. These structures, along with prior functional data, suggest that the isomerization or flipping of the β11-12 linker in the extracellular, ligand-binding domain is an integral component of the desensitization process. To test this, we combined fast perfusion electrophysiology, molecular dynamics simulations and state-dependent non-canonical amino acid cross-linking. We find that both desensitization and recovery can be accelerated by orders of magnitude by mutating resides in this linker or the surrounding region. Furthermore, desensitization can be suppressed by trapping the linker in the resting state, indicating that isomerization of the β11-12 linker is not merely a consequence of, but a necessity for the desensitization process in ASICs.

scholarly journals Automated Quantitative Assessment of Proteins' Biological Function in Protein Knowledge Bases

2008 ◽  
Vol 2008 ◽  
pp. 1-7
Author(s):  
Gabriele Mayr ◽  
Günter Lepperdinger ◽  
Peter Lackner
Keyword(s):  
Functional Data ◽  
Biological Function ◽  
Sequence Data ◽  
Knowledge Bases ◽  
Computer Assisted ◽  
Biological Functions ◽  
Comprehensive Collection ◽  
Quantitative Score ◽  
Protein Sequence Data

Primary protein sequence data are archived in databases together with information regarding corresponding biological functions. In this respect, UniProt/Swiss-Prot is currently the most comprehensive collection and it is routinely cross-examined when trying to unravel the biological role of hypothetical proteins. Bioscientists frequently extract single entries and further evaluate those on a subjective basis. In lieu of a standardized procedure for scoring the existing knowledge regarding individual proteins, we here report about a computer-assisted method, which we applied to score the present knowledge about any given Swiss-Prot entry. Applying this quantitative score allows the comparison of proteins with respect to their sequence yet highlights the comprehension of functional data. pfs analysis may be also applied for quality control of individual entries or for database management in order to rank entry listings.

The yeast potassium transporter TRK2 is able to substitute for TRK1 in its biological function under low K and low pH conditions

Yeast ◽  
2006 ◽  
Vol 23 (8) ◽  
pp. 581-589 ◽  
Author(s):  
Bertha Michel ◽  
Carlos Lozano ◽  
Miriam Rodríguez ◽  
Roberto Coria ◽  
Jorge Ramírez ◽  
...  
Keyword(s):  
Biological Function ◽  
Low Ph ◽  
Potassium Transporter ◽  
Ph Conditions ◽  
Low K
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