ChemInform Abstract: Construction and Function of Interpenetrated Molecules Based on the Positively Charged Axle Components

ChemInform ◽  
2012 ◽  
Vol 43 (39) ◽  
pp. no-no
Author(s):  
Zhi-Jun Zhang ◽  
Yu Liu
Keyword(s):  
And Function ◽  
Positively Charged

scholarly journals Structure of the H1 C-terminal domain and function in chromatin condensationThis paper is one of a selection of papers published in a Special Issue entitled 31st Annual International Asilomar Chromatin and Chromosomes Conference, and has undergone the Journal’s usual peer review process.

2011 ◽  
Vol 89 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Tamara L. Caterino ◽  
Jeffrey J. Hayes
Keyword(s):  
Review Process ◽  
Peer Review Process ◽  
Special Issue ◽  
Direct Role ◽  
Linker Histones ◽  
Terminal Domain ◽  
Chromatin Folding ◽  
And Function ◽  
Positively Charged ◽  
Selection Of

Linker histones are multifunctional proteins that are involved in a myriad of processes ranging from stabilizing the folding and condensation of chromatin to playing a direct role in regulating gene expression. However, how this class of enigmatic proteins binds in chromatin and accomplishes these functions remains unclear. Here we review data regarding the H1 structure and function in chromatin, with special emphasis on the C-terminal domain (CTD), which typically encompasses approximately half of the mass of the linker histone and includes a large excess of positively charged residues. Owing to its amino acid composition, the CTD was previously proposed to function in chromatin as an unstructured polycation. However, structural studies have shown that the CTD adopts detectable secondary structure when interacting with DNA and macromolecular crowding agents. We describe classic and recent experiments defining the function of this domain in chromatin folding and emerging data indicating that the function of this protein may be linked to intrinsic disorder.

scholarly journals A unique kinesin-8 surface loop provides specificity for chromosome alignment

2014 ◽  
Vol 25 (21) ◽  
pp. 3319-3329 ◽  
Author(s):  
Haein Kim ◽  
Cindy Fonseca ◽  
Jason Stumpff
Keyword(s):  
Motor Domain ◽  
Common Mechanism ◽  
Surface Loop ◽  
C Terminus ◽  
Chromosome Alignment ◽  
Spindle Microtubules ◽  
And Function ◽  
Positively Charged ◽  
Mitotic Chromatin

Microtubule length control is essential for the assembly and function of the mitotic spindle. Kinesin-like motor proteins that directly attenuate microtubule dynamics make key contributions to this control, but the specificity of these motors for different subpopulations of spindle microtubules is not understood. Kif18A (kinesin-8) localizes to the plus ends of the relatively slowly growing kinetochore fibers (K-fibers) and attenuates their dynamics, whereas Kif4A (kinesin-4) localizes to mitotic chromatin and suppresses the growth of highly dynamic, nonkinetochore microtubules. Although Kif18A and Kif4A similarly suppress microtubule growth in vitro, it remains unclear whether microtubule-attenuating motors control the lengths of K-fibers and nonkinetochore microtubules through a common mechanism. To address this question, we engineered chimeric kinesins that contain the Kif4A, Kif18B (kinesin-8), or Kif5B (kinesin-1) motor domain fused to the C-terminal tail of Kif18A. Each of these chimeric kinesins localizes to K-fibers; however, K-fiber length control requires an activity specific to kinesin-8s. Mutational studies of Kif18A indicate that this control depends on both its C-terminus and a unique, positively charged surface loop, called loop2, within the motor domain. These data support a model in which microtubule-attenuating kinesins are molecularly “tuned” to control the dynamics of specific subsets of spindle microtubules.

scholarly journals A variant thrombasthenic phenotype associated with compound heterozygosity of integrin β3-subunit: (Met124Val)β3 alters the subunit dimerization rendering a decreased number of constitutive active αIIbβ3 receptors

2004 ◽  
Vol 92 (12) ◽  
pp. 1377-1386 ◽  
Author(s):  
Consuelo González-Manchón ◽  
Nora Butta ◽  
Susana Larrucea ◽  
Elena Arias-Salgado ◽  
Sonia Alonso ◽  
...  
Keyword(s):  
Metal Ion ◽  
Human Platelet ◽  
Cell Aggregation ◽  
Surface Expression ◽  
Paternal Allele ◽  
Constitutive Activity ◽  
Platelet Antigen ◽  
Human Platelet Antigen ◽  
And Function ◽  
Positively Charged

SummaryWe report the analysis of a variant case of thrombasthenic phenotype that is a compound heterozygote for two mutations located within the metal ion dependent adhesion site (MIDAS) of the β3 subunit.The patient inherited a maternal allele carrying the Met124Val substitution and a paternal allele that changes Asp119 to Tyr. Phenotyping of the human platelet antigen 1 (HPA-1) showed that the platelet αIIbβ3 complex in the patient was mostly accounted for by the Asp 119Tyr allele that does not bind to fibrinogen (Fg). The patient showed agonistinduced binding of platelets to Fg but neither binding to PAC-1 nor cell aggregation could be detected, most likely due to the minute expression (≤5%) of αIIb(124Val)β3 receptors. CHO cells expressing (124Val)β3 showed a diminished surface expression of αIIbβ3, enhanced adhesion to immobilized Fg, and spontaneous aggregation in the presence of soluble Fg, suggesting that (124Val)β3 may confer constitutive activity to the αIIb(124Val)β3 receptors. A distinct feature of these cells is the failure of DTT to enhance the binding to soluble Fg and the formation of cell aggregates. The substitution of (124Met)β3 by either a polar or a positively charged amino acid restored the surface exposure and function of the αIIbβ3 receptors whereas a negatively charged residue did not.

scholarly journals Ion counting demonstrates a high electrostatic field generated by the nucleosome

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Magdalena Gebala ◽  
Stephanie L Johnson ◽  
Geeta J Narlikar ◽  
Dan Herschlag
Keyword(s):  
Electrostatic Field ◽  
Nuclear Dna ◽  
Chromatin Organization ◽  
Computational Studies ◽  
Compaction Process ◽  
Histone Protein ◽  
Dna Compaction ◽  
Nucleosome Formation ◽  
And Function ◽  
Positively Charged

In eukaryotes, a first step towards the nuclear DNA compaction process is the formation of a nucleosome, which is comprised of negatively charged DNA wrapped around a positively charged histone protein octamer. Often, it is assumed that the complexation of the DNA into the nucleosome completely attenuates the DNA charge and hence the electrostatic field generated by the molecule. In contrast, theoretical and computational studies suggest that the nucleosome retains a strong, negative electrostatic field. Despite their fundamental implications for chromatin organization and function, these opposing views of nucleosome electrostatics have not been experimentally tested. Herein, we directly measure nucleosome electrostatics and find that while nucleosome formation reduces the complex charge by half, the nucleosome nevertheless maintains a strong negative electrostatic field. Our studies highlight the importance of considering the polyelectrolyte nature of the nucleosome and its impact on processes ranging from factor binding to DNA compaction.

A novel missense mutation in the FGB gene (p.Gly302Arg) leading to afibrinogenemia

2016 ◽  
Vol 36 (S 02) ◽  
pp. S34-S37 ◽  
Author(s):  
H. Rühl ◽  
G. Detarsio ◽  
A. Biswas ◽  
S. Gupta ◽  
M. Davoli ◽  
...  
Keyword(s):  
Missense Mutation ◽  
In Silico ◽  
In Silico Analysis ◽  
Missense Mutations ◽  
The Novel ◽  
Beta Chain ◽  
The Core ◽  
And Function ◽  
Flanking Regions ◽  
Positively Charged

SummaryAfibrinogenemia represents the rarest form of fibrinogen deficiency. Causative missense mutations occur rarely and may improve the understanding of fibrinogen structure and function. Patients and methods: The propositus was a 26-year-old Argentinian with afibrinogenemia. FGA, FGB and FGG exons and flanking regions were screened by sequencing and the mutant protein was analyzed in silico. Results: A novel missense mutation in the FGB gene (Bbeta Gly272Arg, p.Gly302Arg) was identified. In silico analysis revealed its location in a highly conserved region, which preserves the core fold of the C-terminal beta-chain and is important for proper secretion. A substitution by a positively charged large Arg residue in this area would most likely disturb the core fold by additional interactions with adjacent residues (p.Asp291, p.Asp297, p.Asp311), or by forming of non-native interactions with other proteins, thereby hindering the action of molecular chaperones. Both alternatives would disturb the regular secretion of the beta-chain. Conclusions: The novel mis-sense mutation in the FGB gene causes afibrinogenemia most probably by affecting the secretion of the fibrinogen beta-chain.

scholarly journals Non-equivalence of Key Positively Charged Residues of the Free Fatty Acid 2 Receptor in the Recognition and Function of AgonistVersusAntagonist Ligands

2015 ◽  
Vol 291 (1) ◽  
pp. 303-317 ◽  
Author(s):  
Eugenia Sergeev ◽  
Anders Højgaard Hansen ◽  
Sunil K. Pandey ◽  
Amanda E. MacKenzie ◽  
Brian D. Hudson ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Charged Residues ◽  
And Function ◽  
Positively Charged

scholarly journals Calreticulin mutants as oncogenic rogue chaperones for TpoR and traffic-defective pathogenic TpoR mutants

Blood ◽  
2019 ◽  
Vol 133 (25) ◽  
pp. 2669-2681 ◽  
Author(s):  
Christian Pecquet ◽  
Ilyas Chachoua ◽  
Anita Roy ◽  
Thomas Balligand ◽  
Gaëlle Vertenoeil ◽  
...  
Keyword(s):  
Cell Surface ◽  
Secretory Pathway ◽  
Myeloproliferative Neoplasms ◽  
Charged Amino Acids ◽  
Thrombopoietin Receptor ◽  
Surface Localization ◽  
Exon 9 ◽  
Cell Surface Localization ◽  
And Function ◽  
Positively Charged

Abstract Calreticulin (CALR) +1 frameshift mutations in exon 9 are prevalent in myeloproliferative neoplasms. Mutant CALRs possess a new C-terminal sequence rich in positively charged amino acids, leading to activation of the thrombopoietin receptor (TpoR/MPL). We show that the new sequence endows the mutant CALR with rogue chaperone activity, stabilizing a dimeric state and transporting TpoR and mutants thereof to the cell surface in states that would not pass quality control; this function is absolutely required for oncogenic transformation. Mutant CALRs determine traffic via the secretory pathway of partially immature TpoR, as they protect N117-linked glycans from further processing in the Golgi apparatus. A number of engineered or disease-associated TpoRs such as TpoR/MPL R102P, which causes congenital thrombocytopenia, are rescued for traffic and function by mutant CALRs, which can also overcome endoplasmic reticulum retention signals on TpoR. In addition to requiring N-glycosylation of TpoR, mutant CALRs require a hydrophobic patch located in the extracellular domain of TpoR to induce TpoR thermal stability and initial intracellular activation, whereas full activation requires cell surface localization of TpoR. Thus, mutant CALRs are rogue chaperones for TpoR and traffic-defective TpoR mutants, a function required for the oncogenic effects.

scholarly journals Assessment of Interaction of Human OCT 1-3 Proteins and Metformin Using Silico Analyses

2020 ◽  
Vol 67 (4) ◽  
pp. 1202-1215
Author(s):  
Faruk Berat Akçeşme ◽  
Nail Beşli ◽  
Jorge Peña-García ◽  
Horacio Pérez-Sánchez
Keyword(s):  
3D Structure ◽  
Organic Cation Transporter ◽  
Dynamics Simulation ◽  
Diabetic Patients ◽  
Docking Simulations ◽  
Functional Regions ◽  
Ligand Binding Sites ◽  
And Function ◽  
Predicted Binding Site ◽  
Positively Charged

Metformin, a drug frequently used by diabetic patients as the first-line treatment worldwide, is positively charged and is transported into the cell through human organic cation transporter (hOCT 1-3) proteins. We aimed to mimic the cellular uptake of metformin by hOCT1-3 with various bioinformatics methods and tools. 3D structure of OCT1-3 proteins was predicted by considering the structures and function of these proteins. We predicted functional regions (active and ligand binding sites) of OCT1-3 and performed comparative bioinformatics analysis. The predicted structure of hOCT1-3 was then analyzed in the Blind Docking server and the results were confirmed with predicted binding site residues and conserved domain regions. We simulated the OCT1-3 and metformin docking and also validated the docking procedure with other substrates of HOCT1-3 proteins. We selected the best poses of metformin docking simulations as per binding energy (–5.27 to –4.60 kcal/mol). Lastly, we validated the static description of protein-ligand (OCT-Metformin) interactions by performing molecular dynamics simulation. Eventually, we obtained stable simulation of OCT-metformin interaction.

The Disposition of Proteinpoly-Saccharide in the Epiphysial Plate Cartilage of the Young Rabbit

1970 ◽  
Vol 6 (3) ◽  
pp. 843-864
Author(s):  
J. W. SMITH
Keyword(s):  
Uranyl Acetate ◽  
Bismuth Nitrate ◽  
Young Rabbit ◽  
Proliferative Zone ◽  
Attachment Sites ◽  
Central Regions ◽  
The Matrix ◽  
And Function ◽  
Initial Mineral ◽  
Positively Charged

Although acidic bismuth nitrate stains the polysaccharide in the unfixed bovine epiphysial plate, it fails to do so in that of the rabbit. After fixation in glutaraldehyde, however, Araldite sections stained with bismuth nitrate exhibit 3-nm spots which are interpreted as polysaccharide chains in coiled conformation. In the matrix of the proliferative zone, and in the large Golgi vesicles of the associated chondrocytes, the polysaccharide spots are arranged in closely packed groups. Lead citrate and uranyl acetate staining shows the non-fibrillar material in these situations as a continuous network of particles. The centre of each particle is translucent, and double staining with phosphotungstic acid and bismuth indicates that these central regions contain the groups of polysaccharide spots. It is suggested that in the unfixed tissue bismuth binding is prevented by screening of the polysaccharide sulphates by positively charged non-collagenous protein, and that fixation, by precipitating this protein as a network around groups of proteinpolysaccharide molecules, frees the sulphate groups to react with bismuth. Proteinpolysaccharide molecules appear to be tangentially attached to each period of the small collagen fibrils of the matrix. Fixation precipitation of the associated protein tends to aggregate these molecules into groups which are often somewhat eccentric to their original attachment sites, and consequently the fibrillar attachment of proteinpolysaccharide usually appears to be rather irregular. In the zone of early calcification single mineral crystals are associated with dense bodies of unknown nature and function. Many are also associated with short linear rows of polysaccharide spots. This and the similarity in the lengths of the two structures suggest that initial mineral crystals may grow along a proteinpolysaccharide molecule from one end to the other. Absence of polysaccharide spots in relation to crystal clusters suggest that these clusters are formed as a result of the seeding effect of the initial single crystals.

A Review Study of Dendrimer Nanoparticles Influences on Stored Platelet in Order to Treat Patients (2001-2020)

2021 ◽  
Vol 17 ◽  
Author(s):  
Tahereh Zadeh Mehrizi ◽  
Mehdi Shafiee Ardestani ◽  
Sedigheh Amini Kafiabad
Keyword(s):  
Molecular Weight ◽  
Storage Time ◽  
Storage Temperature ◽  
Storage Conditions ◽  
Normal Function ◽  
Platelet Storage ◽  
Review Study ◽  
And Function ◽  
Positively Charged

Background: Platelets are sensitive to chilling, therefore, the optimal storage temperature for maintaining normal function and structure in platelets is 22-24 °C up to 3-5 days. Introduction: Platelets are important blood cells involved in immunity, inflammation, and thrombosis. Today, platelet products are widely used to prevent bleeding in patients with thrombocytopenia and coagulopathy disorders. As a result, maintaining the quality of these products is very important. Method: In this review study, the reported influences of various dendrimers on platelets from 2001 to 2020 were investigated. Result: The results showed that positively charged dendrimers could cause platelet aggregation and activation during platelet storage time through their amine residues. In addition to surface charge, high generations, molecular weight and concentration are not recommended in the field of platelet storage and treatment. In contrast, negatively charged dendrimers, usually used at lower generations with proper molecular weight, lower size (less than 100 nm) and their carboxyl residues, cannot induce adverse effects on platelets during storage time. In addition, the results of this study revealed that PEGylation of dendrimers and platelets could improve platelet storage conditions. Conclusion: As anionic dendrimers can improve platelet storage time without inducing significant changes in morphology and function of platelets, they are recommended in the field of platelet storage and treatment.

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