scholarly journals The contribution of hydrophobic residues in the pore-forming region of the ryanodine receptor channel to block by large tetraalkylammonium cations and Shaker B inactivation peptides

2012 ◽  
Vol 140 (3) ◽  
pp. 325-339 ◽  
Author(s):  
Sammy A. Mason ◽  
Cedric Viero ◽  
Joanne Euden ◽  
Mark Bannister ◽  
Duncan West ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Hydrophobic Interactions ◽  
Structural Information ◽  
Dissociation Rate ◽  
Structural Components ◽  
Hydrophobic Residues ◽  
K Channels ◽  
New Information ◽  
Tetraalkylammonium Cations ◽  
Cytosolic Side

Although no high-resolution structural information is available for the ryanodine receptor (RyR) channel pore-forming region (PFR), molecular modeling has revealed broad structural similarities between this region and the equivalent region of K+ channels. This study predicts that, as is the case in K+ channels, RyR has a cytosolic vestibule lined with predominantly hydrophobic residues of transmembrane helices (TM10). In K+ channels, this vestibule is the binding site for blocking tetraalkylammonium (TAA) cations and Shaker B inactivation peptides (ShBPs), which are stabilized by hydrophobic interactions involving specific residues of the lining helices. We have tested the hypothesis that the cytosolic vestibule of RyR fulfils a similar role and that TAAs and ShBPs are stabilized by hydrophobic interactions with residues of TM10. Both TAAs and ShBPs block RyR from the cytosolic side of the channel. By varying the composition of TAAs and ShBPs, we demonstrate that the affinity of both species is determined by their hydrophobicity, with variations reflecting alterations in the dissociation rate of the bound blockers. We investigated the role of TM10 residues of RyR by monitoring block by TAAs and ShBPs in channels in which the hydrophobicity of individual TM10 residues was lowered by alanine substitution. Although substitutions changed the kinetics of TAA interaction, they produced no significant changes in ShBP kinetics, indicating the absence of specific hydrophobic sites of interactions between RyR and these peptides. Our investigations (a) provide significant new information on both the mechanisms and structural components of the RyR PFR involved in block by TAAs and ShBPs, (b) highlight important differences in the mechanisms and structures determining TAA and ShBP block in RyR and K+ channels, and (c) demonstrate that although the PFRs of these channels contain analogous structural components, significant differences in structure determine the distinct ion-handling properties of the two species of channel.

Lung morphometry: a new generation of tools and experiments for organ, tissue, cell, and molecular biology

1993 ◽  
Vol 265 (6) ◽  
pp. L521-L548 ◽  
Author(s):  
R. P. Bolender ◽  
D. M. Hyde ◽  
R. T. Dehoff
Keyword(s):  
Structural Information ◽  
Dimensional Space ◽  
Three Dimensional ◽  
Biological Data ◽  
Theory And Practice ◽  
Tissue Cell ◽  
New Information ◽  
Organ Tissue ◽  
New Generation ◽  
Three Dimensional Space

Today all structural information of the lung can be quantified and interpreted in the three-dimensional space of real-world biology. Remarkable achievements in the theory and practice of biological stereology are creating a new generation of data suitable for constructing structural hierarchies. Such hierarchies serve to organize and link biological data, thereby providing a framework on which to build new information systems. In this review, we describe the new tools of quantitative morphology and show how they can be used to design new experiments for lung research.

Morphogenetic Updating Algorithm and its Application in Updating Probabilistic Risk

2019 ◽  
Vol 33 (07) ◽  
pp. 1950008
Author(s):  
Jing Tian ◽  
Germano Resconi
Keyword(s):  
Risk Analysis ◽  
Structural Information ◽  
Guangdong Province ◽  
Special Problem ◽  
Internal Source ◽  
The Core ◽  
Dynamic Risk ◽  
New Information ◽  
Cosine Similarity Measure ◽  
Probabilistic Risk

The problem of risk update is one of the core problems of dynamic risk analysis. As for updating widely used probabilistic risk, it’s a kind of special problem of pattern recognition which means to transfer from old pattern to new pattern with new information. Aiming at updating probabilistic risk only with the new observations and without the original observations, this paper proposes the morphogenetic updating algorithm to update the probabilistic risk with only new observations and old risk values by reproducing the morphogenesis of new observations and old risk values based on morphogenetic estimation. The form rules hidden in the risk values and new observations are discovered by internal source in Write operation, and the projection of the input and the cosine similarity measure as the basis for defining the weight of updating are computed in Read operation. Based on Resconi theorem, the input is reproduced by its projection on the context which provides the same mathematical space for updating and stores the structural information hidden in the risk. By applying the algorithm to updating the probabilistic risk of typhoon rainstorms occurred in Guangdong Province, it proves that morphogenetic updating algorithm provides us a method to updating probabilistic risk fast and satisfactorily and it’s a sustainable updating method which can be used for dynamic risk analysis.

scholarly journals Effect of Hydrophobic Interactions on Lower Critical Solution Temperature for Poly(N-isopropylacrylamide-co-dopamine Methacrylamide) Copolymers

Polymers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 991 ◽  
Author(s):  
Alberto García-Peñas ◽  
Chandra Sekhar Biswas ◽  
Weijun Liang ◽  
Yu Wang ◽  
Pianpian Yang ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Lower Critical Solution Temperature ◽  
Hydrophobic Interactions ◽  
Structural Information ◽  
Drug Carriers ◽  
Solution Temperature ◽  
Polymerization Degree ◽  
Tissue Engineering Scaffolds ◽  
Critical Solution Temperature ◽  
Precise Control

For the preparation of thermoresponsive copolymers, for e.g., tissue engineering scaffolds or drug carriers, a precise control of the synthesis parameters to set the lower critical solution temperature (LCST) is required. However, the correlations between molecular parameters and LCST are partially unknown and, furthermore, LCST is defined as an exact temperature, which oversimplifies the real situation. Here, random N-isopropylacrylamide (NIPAM)/dopamine methacrylamide (DMA) copolymers were prepared under a systematical variation of molecular weight and comonomer amount and their LCST in water studied by calorimetry, turbidimetry, and rheology. Structural information was deduced from observed transitions clarifying the contributions of molecular weight, comonomer content, end-group effect or polymerization degree on LCST, which were then statistically modeled. This proved that the LCST can be predicted through molecular structure and conditions of the solutions. While the hydrophobic DMA lowers the LCST especially the onset, polymerization degree has an important but smaller influence over all the whole LCST range.

scholarly journals Prediction and Analysis of Surface Hydrophobic Residues in Tertiary Structure of Proteins

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Shambhu Malleshappa Gowder ◽  
Jhinuk Chatterjee ◽  
Tanusree Chaudhuri ◽  
Kusum Paul
Keyword(s):  
Tertiary Structure ◽  
Structural Information ◽  
Solvent Accessibility ◽  
Conservation Score ◽  
Protein Structures ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Data Set ◽  
Hydrophobic Residues ◽  
Monomeric Proteins

The analysis of protein structures provides plenty of information about the factors governing the folding and stability of proteins, the preferred amino acids in the protein environment, the location of the residues in the interior/surface of a protein and so forth. In general, hydrophobic residues such as Val, Leu, Ile, Phe, and Met tend to be buried in the interior and polar side chains exposed to solvent. The present work depends on sequence as well as structural information of the protein and aims to understand nature of hydrophobic residues on the protein surfaces. It is based on the nonredundant data set of 218 monomeric proteins. Solvent accessibility of each protein was determined using NACCESS software and then obtained the homologous sequences to understand how well solvent exposed and buried hydrophobic residues are evolutionarily conserved and assigned the confidence scores to hydrophobic residues to be buried or solvent exposed based on the information obtained from conservation score and knowledge of flanking regions of hydrophobic residues. In the absence of a three-dimensional structure, the ability to predict surface accessibility of hydrophobic residues directly from the sequence is of great help in choosing the sites of chemical modification or specific mutations and in the studies of protein stability and molecular interactions.

scholarly journals Charybdotoxin block of single Ca2+-activated K+ channels. Effects of channel gating, voltage, and ionic strength.

1988 ◽  
Vol 91 (3) ◽  
pp. 317-333 ◽  
Author(s):  
C S Anderson ◽  
R MacKinnon ◽  
C Smith ◽  
C Miller
Keyword(s):  
Ionic Strength ◽  
Plasma Membranes ◽  
Scorpion Venom ◽  
Dissociation Rate ◽  
K Channel ◽  
Single Channels ◽  
Association Rate ◽  
Open Probability ◽  
Apparent Dissociation Constant ◽  
K Channels

Charybdotoxin (CTX), a small, basic protein from scorpion venom, strongly inhibits the conduction of K ions through high-conductance, Ca2+-activated K+ channels. The interaction of CTX with Ca2+-activated K+ channels from rat skeletal muscle plasma membranes was studied by inserting single channels into uncharged planar phospholipid bilayers. CTX blocks K+ conduction by binding to the external side of the channel, with an apparent dissociation constant of approximately 10 nM at physiological ionic strength. The dwell-time distributions of both blocked and unblocked states are single-exponential. The toxin association rate varies linearly with the CTX concentration, and the dissociation rate is independent of it. CTX is competent to block both open and closed channels; the association rate is sevenfold faster for the open channel, while the dissociation rate is the same for both channel conformations. Membrane depolarization enhances the CTX dissociation rate e-fold/28 mV; if the channel's open probability is maintained constant as voltage varies, then the toxin association rate is voltage independent. Increasing the external solution ionic strength from 20 to 300 mM (with K+, Na+, or arginine+) reduces the association rate by two orders of magnitude, with little effect on the dissociation rate. We conclude that CTX binding to the Ca2+-activated K+ channel is a bimolecular process, and that the CTX interaction senses both voltage and the channel's conformational state. We further propose that a region of fixed negative charge exists near the channel's CTX-binding site.

scholarly journals Defining the Ail Ligand-Binding Surface: Hydrophobic Residues in Two Extracellular Loops Mediate Cell and Extracellular Matrix Binding To Facilitate Yop Delivery

2017 ◽  
Vol 85 (4) ◽  
Author(s):  
Tiffany M. Tsang ◽  
Jeffrey S. Wiese ◽  
Jamal A. Alhabeil ◽  
Lisa D. Usselman ◽  
Joshua J. Thomson ◽  
...  
Keyword(s):  
Hydrophobic Interactions ◽  
Binding Activity ◽  
Host Cells ◽  
Cell Binding ◽  
Content Type ◽  
Mutant Proteins ◽  
Hydrophobic Residues ◽  
Extracellular Loops ◽  
Binding Surface ◽  
Mediate Cell

ABSTRACT Yersinia pestis, the causative agent of plague, binds host cells to deliver cytotoxic Yop proteins into the cytoplasm that prevent phagocytosis and generation of proinflammatory cytokines. Ail is an eight-stranded β-barrel outer membrane protein with four extracellular loops that mediates cell binding and resistance to human serum. Following the deletion of each of the four extracellular loops that potentially interact with host cells, the Ail-Δloop 2 and Ail-Δloop 3 mutant proteins had no cell-binding activity while Ail-Δloop 4 maintained cell binding (the Ail-Δloop 1 protein was unstable). Using the codon mutagenesis scheme SWIM (selection without isolation of mutants), we identified individual residues in loops 1, 2, and 3 that contribute to host cell binding. While several residues contributed to the binding of host cells and purified fibronectin and laminin, as well as Yop delivery, three mutations, F80A (loop 2), S128A (loop 3), and F130A (loop 3), produced particularly severe defects in cell binding. Combining these mutations led to an even greater reduction in cell binding and severely impaired Yop delivery with only a slight defect in serum resistance. These findings demonstrate that Y. pestis Ail uses multiple extracellular loops to interact with substrates important for adhesion via polyvalent hydrophobic interactions.

scholarly journals Electrostatic and Hydrophobic Interactions Differentially Tune Membrane Binding Kinetics of the C2 Domain of Protein Kinase Cα

2013 ◽  
Vol 288 (23) ◽  
pp. 16905-16915 ◽  
Author(s):  
Angela M. Scott ◽  
Corina E. Antal ◽  
Alexandra C. Newton
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase ◽  
Rate Constants ◽  
Electrostatic Interactions ◽  
Hydrophobic Interactions ◽  
Dissociation Rate ◽  
C2 Domain ◽  
Pkc Isozymes ◽  
Dissociation Rate Constants

The cellular activation of conventional protein kinase C (PKC) isozymes is initiated by the binding of their C2 domains to membranes in response to elevations in intracellular Ca2+. Following this C2 domain-mediated membrane recruitment, the C1 domain binds its membrane-embedded ligand diacylglycerol, resulting in activation of PKC. Here we explore the molecular mechanisms by which the C2 domain controls the initial step in the activation of PKC. Using stopped-flow fluorescence spectroscopy to measure association and dissociation rate constants, we show that hydrophobic interactions are the major driving force in the binding of the C2 domain to anionic membranes, whereas electrostatic interactions dominate in membrane retention. Specifically, mutation of select hydrophobic or select basic residues in the Ca2+-binding loops reduces membrane affinity by distinct mechanisms; mutation of hydrophobic residues primarily alters association rate constants, whereas mutation of charged residues affects dissociation rate constants. Live cell imaging reveals that introduction of these mutations into full-length PKCα not only reduces the Ca2+-dependent translocation to plasma membrane but, by impairing the plasma membrane-sensing role of the C2 domain, causes phorbol ester-triggered redistribution of PKCα to other membranes, such as the Golgi. These data underscore the key role of the C2 domain in driving conventional PKC isozymes to the plasma membrane and reveal that not only the amplitude but also the subcellular location of conventional PKC signaling can be tuned by altering the affinity of this module for membranes.

scholarly journals Potassium blocks barium permeation through a calcium-activated potassium channel.

1988 ◽  
Vol 92 (5) ◽  
pp. 549-567 ◽  
Author(s):  
J Neyton ◽  
C Miller
Keyword(s):  
Skeletal Muscle ◽  
Lipid Bilayers ◽  
Dissociation Rate ◽  
Planar Lipid Bilayers ◽  
Rat Skeletal Muscle ◽  
K Channels ◽  
Calcium Activated Potassium Channel ◽  
Micromolar Range ◽  
High Conductance ◽  
External K

Single high-conductance Ca2+-activated K+ channels from rat skeletal muscle were inserted into planar lipid bilayers, and discrete blocking by the Ba2+ ion was studied. Specifically, the ability of external K+ to reduce the Ba2+ dissociation rate was investigated. In the presence of 150 mM internal K+, 1-5 microM internal Ba2+, and 150 mM external Na+, Ba2+ dissociation is rapid (5 s-1) in external solutions that are kept rigorously K+ free. The addition of external K+ in the low millimolar range reduces the Ba2+ off-rate 20-fold. Other permeant ions, such as Tl+, Rb+, and NH4+ show a similar effect. The half-inhibition constants rise in the order: Tl+ (0.08 mM) less than Rb+ (0.1 mM) less than K+ (0.3 mM) less than Cs+ (0.5 mM) less than NH4+ (3 mM). When external Na+ is replaced by 150 mM N-methyl glucamine, the Ba2+ off-rate is even higher, 20 s-1. External K+ and other permeant ions reduce this rate by approximately 100-fold in the micromolar range of concentrations. Na+ also reduces the Ba2+ off-rate, but at much higher concentrations. The half-inhibition concentrations rise in the order: Rb+ (4 microM) less than K+ (19 microM) much less than Na+ (27 mM) less than Li+ (greater than 50 mM). The results require that the conduction pore of this channel contains at least three sites that may all be occupied simultaneously by conducting ions.

scholarly journals Advantages of Colour Etching in Quality Control of Recycled Al-Si Cast Alloys

2019 ◽  
Vol 1 (1) ◽  
pp. 296-303
Author(s):  
Eva Tillová ◽  
Lenka Kuchariková ◽  
Mária Chalupová ◽  
Juraj Belan ◽  
Alan Vaško ◽  
...  
Keyword(s):  
Quality Control ◽  
Cast Alloy ◽  
Structural Components ◽  
Microscopic Appearance ◽  
Structure Information ◽  
Casting Quality ◽  
Colour Contrast ◽  
New Information ◽  
Cast Alloys ◽  
Two Phases

Abstract Colour Metallography is a set of light metallographic microscopy methodologies that utilize phase colour contrast as a source of new structure information compared to conventional techniques. In many cases, colour contrast can be induced where no identifiable phase contrast is obtained by conventional techniques. With the help of colour contrast, we gain new information on the structure of Al-Si alloys, especially intermetallic phases, in which the benefits of its use in casting quality control are of benefit. Blue-yellow contrast is definitely more pronounced than dark grey or light grey contrast. There is no substantial reproducible colour reproduction, since it is irrelevant whether the two phases are distinguished by blue-yellow or green-ocher contrast. When using the colour contrast, the structural components differ not only according to their microscopic appearance, but also based on the knowledge of the chemical composition of alloys, interactions between structural components, knowledge of the possible influence of Al-alloys structure (e.g. refining, modifications, heat treatment). Colour contrast in quality control of Al-Si alloys was applied to AlSiMg cast alloy (AlSi7Mg0.3; AlSi7MgTi; AlSi10MgMn; etc.)

scholarly journals From molecular modules to modular materials

2004 ◽  
Vol 76 (10) ◽  
pp. 1847-1867 ◽  
Author(s):  
D. G. Kurth ◽  
Shaoqin Liu ◽  
D. Volkmer
Keyword(s):  
Hydrophobic Interactions ◽  
Current Understanding ◽  
Structural Components ◽  
Molecular Materials ◽  
Electrostatic And Hydrophobic Interactions

The combination of metallosupramolecular modules (MEMOs) as functional and amphiphiles as structural components is presented in detail to illustrate our current understanding of encapsulation using surfactants, lipids, and dendrimers. The simplicity of fabrication and the availability of the starting components allow this technique as an attractive tool to create new nanoscale molecular materials. The interaction of amphiphiles and MEMOs occurs spontaneously and is driven by the release of counterions as well as electrostatic and hydrophobic interactions.

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