scholarly journals Cross-linking of DNA Segments by Histone H1 Explains H1 Associated Phenomena of Chromatin Folding

2019 ◽  
Vol 1 (2) ◽  
pp. 6-10
Author(s):  
Qazi Hamid ◽  
Ojaswee Dahal ◽  
Osama Dasti ◽  
Ziledar Ali
Keyword(s):  
Molecular Mechanism ◽  
Salt Bridge ◽  
Histone H1 ◽  
Cross Linking ◽  
Cooperative Binding ◽  
Interphase Chromatin ◽  
Phosphodiester Bonds ◽  
Arginine Residues ◽  
Chromatin Folding ◽  
Positively Charged

Molecular mechanism for the cooperative and non-cooperative binding of histone H1 to DNA, its rearrangement and exchange between chromatin fibers and its role in the folding of interphase chromatin are proposed in this communication. The mechanism of H1 binding to DNA described here is simple and is based on two established facts; (i) histone H1 can crosslink two DNA segments through salt bridge formation between its positively charged lysine and arginine residues and the negatively charged phosphodiester bonds of the DNA segments, (ii) cations reduce the negative charges on DNA segments and thus decrease the force of repulsion between them.

Multilayer composite beads constructed via layer-by-layer self-assembly for lysozyme controlled release

RSC Advances ◽  
2014 ◽  
Vol 4 (46) ◽  
pp. 24369-24376 ◽  
Author(s):  
Jiemin Zhao ◽  
Xiaoping Wang ◽  
Yanshen Kuang ◽  
Yufeng Zhang ◽  
Xiaowen Shi ◽  
...  
Keyword(s):  
Controlled Release ◽  
Self Assembly ◽  
Cross Linking ◽  
Layer By Layer ◽  
Multilayer Composite ◽  
Composite Beads ◽  
Assembly Technique ◽  
Positively Charged

Alginate (ALG)–lysozyme (LZ) beads were fabricated by a cross-linking process. Negatively charged ALG and positively charged LZ were alternately deposited on the positively charged ALG–LZ beads via a layer-by-layer (LBL) self-assembly technique.

Role of S4 positively charged residues in the regulation of Kv4.3 inactivation and recovery

2007 ◽  
Vol 293 (3) ◽  
pp. C906-C914 ◽  
Author(s):  
Matthew R. Skerritt ◽  
Donald L. Campbell
Keyword(s):  
Positive Charge ◽  
Voltage Sensitivity ◽  
Shaker Channels ◽  
Recovery From Inactivation ◽  
Kv4 Channels ◽  
Charged Residues ◽  
Arginine Residues ◽  
Voltage Sensing Domain ◽  
Positively Charged

The molecular and biophysical mechanisms by which voltage-sensitive K+ (Kv)4 channels inactivate and recover from inactivation are presently unresolved. There is a general consensus, however, that Shaker-like N- and P/C-type mechanisms are likely not involved. Kv4 channels also display prominent inactivation from preactivated closed states [closed-state inactivation (CSI)], a process that appears to be absent in Shaker channels. As in Shaker channels, voltage sensitivity in Kv4 channels is thought to be conferred by positively charged residues localized to the fourth transmembrane segment (S4) of the voltage-sensing domain. To investigate the role of S4 positive charge in Kv4.3 gating transitions, we analyzed the effects of charge elimination at each positively charged arginine (R) residue by mutation to the uncharged residue alanine (A). We first demonstrated that R290A, R293A, R296A, and R302A mutants each alter basic activation characteristics consistent with positive charge removal. We then found strong evidence that recovery from inactivation is coupled to deactivation, showed that the precise location of the arginine residues within S4 plays an important role in the degree of development of CSI and recovery from CSI, and demonstrated that the development of CSI can be sequentially uncoupled from activation by R296A, specifically. Taken together, these results extend our current understanding of Kv4.3 gating transitions.

Formaldehyde cross-linking and immunoprecipitation demonstrate developmental changes in H1 association with transcriptionally active genes

1991 ◽  
Vol 11 (3) ◽  
pp. 1729-1733
Author(s):  
P C Dedon ◽  
J A Soults ◽  
C D Allis ◽  
M A Gorovsky
Keyword(s):  
Transcriptional Activity ◽  
Inverse Correlation ◽  
Dna Interaction ◽  
Histone H1 ◽  
Developmental Changes ◽  
Cross Linking ◽  
Developmental States ◽  
Logarithmic Growth ◽  
Active Genes

The in vivo association of histone H1 with specific genes in Tetrahymena thermophila was studied by using a simplified cross-linking and immunoprecipitation technique. Four genes were analyzed whose activities vary in three different developmental states (logarithmic growth, starvation, and conjugation). Hybridization of the immunoprecipitated DNA to cloned probes showed an inverse correlation between the level of immunoprecipitation with H1 antiserum and transcriptional activity. This represents the first demonstration of an alteration in histone H1-DNA interaction associated with developmental changes in transcriptional activity.

Modifications of Extrinsic Pathway Inhibitor (EPI) and Factor Xa that Affect their Ability to Interact and to Inhibit Factor Vila/Tissue Factor: Evidence for a Two-Step Model of Inhibition

1988 ◽  
Vol 60 (03) ◽  
pp. 453-456 ◽  
Author(s):  
Bonnie J Warn-Cramer ◽  
L Vijaya Mohan Rao ◽  
Steven L Maki ◽  
Samuel I Rapaport
Keyword(s):  
Tissue Factor ◽  
Factor Viia ◽  
Factor Xa ◽  
Extrinsic Pathway ◽  
Step Model ◽  
Arginine Residues ◽  
Gla Domain ◽  
Positively Charged ◽  
Independent Reaction ◽  
Inhibit Factor

SummaryInhibition of factor VIIa/tissue factor (TF) by extrinsic pathway inhibitor (EPI) requires the participation of factor Xa. Through this inhibition, factor Xa generated initially may feed back to suppress continuing generation of factor Xa via the extrinsic pathway during hemostasis. We have utilized chemical modifications of EPI and factor Xa to study the reactions responsible for inhibition. The data are consistent with a two-step model. First, EPI binds to factor Xa in a Ca2+ independent reaction in which the gla-domain of factor Xa does not participate. A functional active site on factor Xa and arginine residues on EPI are essential for this step. Then the factor Xa/EPI complex binds to factor VIIa/TF with resultant inhibition of its enzymatic activity. The gla-domain of factor Xa is essential for this step. Intact positively charged lysines on factor Xa may also be important

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 The ABCG2 multidrug transporter is a pump gated by a valve and an extracellular lid

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Narakorn Khunweeraphong ◽  
Daniel Szöllősi ◽  
Thomas Stockner ◽  
Karl Kuchler
Keyword(s):  
Drug Release ◽  
Molecular Mechanism ◽  
Salt Bridge ◽  
Multidrug Transporter ◽  
Peristaltic Pump ◽  
Disulfide Bridges ◽  
Control Drug ◽  
Atp Binding Cassette Transporter ◽  
Extracellular Loops ◽  
Control Drug Release

AbstractThe human ATP-binding cassette transporter ABCG2 is a key to anticancer resistance and physiological detoxification. However, the molecular mechanism of substrate transport remains enigmatic. A hydrophobic di-leucine motif in the ABCG2 core separates a large intracellular cavity from a smaller upper cavity. We show that the di-leucine motif acts as a valve that controls drug extrusion. Moreover, the extracellular structure engages the re-entry helix and all extracellular loops to form a roof architecture on top of the upper cavity. Disulfide bridges and a salt bridge limit roof flexibility, but provide a lid-like function to control drug release. We propose that drug translocation from the central to the upper cavities through the valve is driven by a squeezing motion, suggesting that ABCG2 operates similar to a peristaltic pump. Finally, the roof contains essential residues, offering therapeutic options to block ABCG2 by either targeting the valve or essential residues in the roof.

Intrinsic gating mechanisms of epithelial sodium channels

2002 ◽  
Vol 283 (2) ◽  
pp. C646-C650 ◽  
Author(s):  
Hong-Long Ji ◽  
Catherine M. Fuller ◽  
Dale J. Benos
Keyword(s):  
Sodium Channels ◽  
Xenopus Oocytes ◽  
Transmembrane Domain ◽  
Receptor Site ◽  
Epithelial Sodium Channels ◽  
Gating Mechanisms ◽  
Putative Receptor ◽  
Arginine Residues ◽  
Insight Into ◽  
Positively Charged

The hypothesis that there is a highly conserved, positively charged region distal to the second transmembrane domain in α-ENaC (epithelial sodium channel) that acts as a putative receptor site for the negatively charged COOH-terminal β- and γ-ENaC tails was tested in mutagenesis experiments. After expression in Xenopus oocytes, α-ENaC constructs in which positively charged arginine residues were converted into negatively charged glutamic acids could not be inhibited by blocking peptides. These observations provide insight into the gating machinery of ENaC.

scholarly journals Role of Arginines in Coenzyme A Binding and Catalysis by the Phosphotransacetylase from Methanosarcina thermophila

2001 ◽  
Vol 183 (14) ◽  
pp. 4244-4250 ◽  
Author(s):  
Prabha P. Iyer ◽  
James G. Ferry
Keyword(s):  
Active Site ◽  
Coenzyme A ◽  
Sulfhydryl Group ◽  
Salt Bridge ◽  
Competitive Inhibitor ◽  
Enzyme Inactivation ◽  
Methanosarcina Thermophila ◽  
Arginine Residues ◽  
Substrate Protection

ABSTRACT Phosphotransacetylase (EC 2.3.1.8 ) catalyzes the reversible transfer of the acetyl group from acetyl phosphate to coenzyme A (CoA): CH3COOPO3 2− + CoASH ⇆ CH3COSCoA + HPO4 2−. The role of arginine residues was investigated for the phosphotransacetylase from Methanosarcina thermophila. Kinetic analysis of a suite of variants indicated that Arg 87 and Arg 133 interact with the substrate CoA. Arg 87 variants were reduced in the ability to discriminate between CoA and the CoA analog 3′-dephospho-CoA, indicating that Arg 87 forms a salt bridge with the 3′-phosphate of CoA. Arg 133 is postulated to interact with the 5′-phosphate of CoA. Large decreases in k cat andk cat/Km for all of the Arg 87 and Arg 133 variants indicated that these residues are also important, although not essential, for catalysis. Large decreases ink cat andk cat/Km were also observed for the variants in which lysine replaced Arg 87 and Arg 133, suggesting that the bidentate interaction of these residues with CoA or their greater bulk is important for optimal activity. Desulfo-CoA is a strong competitive inhibitor of the enzyme, suggesting that the sulfhydryl group of CoA is important for the optimization of CoA-binding energy but not for tight substrate binding. Chemical modification of the wild-type enzyme by 2,3-butanedione and substrate protection by CoA indicated that at least one reactive arginine is in the active site and is important for activity. The inhibition pattern of the R87Q variant indicated that Arg 87 is modified, which contributes to the inactivation; however, at least one additional active-site arginine is modified leading to enzyme inactivation, albeit at a lower rate.

scholarly journals Poly-Arginine and Arginine-Rich Peptides are Neuroprotective in Stroke Models

2015 ◽  
Vol 35 (6) ◽  
pp. 993-1004 ◽  
Author(s):  
Bruno P Meloni ◽  
Laura M Brookes ◽  
Vince W Clark ◽  
Jane L Cross ◽  
Adam B Edwards ◽  
...  
Keyword(s):  
Glutamic Acid ◽  
Calcium Influx ◽  
Neuroprotective Effect ◽  
Glucose Deprivation ◽  
Cell Penetrating Peptides ◽  
Neuronal Cultures ◽  
Stroke Models ◽  
Arginine Residues ◽  
Positively Charged ◽  
Peptide Treatment

Using cortical neuronal cultures and glutamic acid excitotoxicity and oxygen-glucose deprivation (OGD) stroke models, we demonstrated that poly-arginine and arginine-rich cell-penetrating peptides (CPPs), are highly neuroprotective, with efficacy increasing with increasing arginine content, have the capacity to reduce glutamic acid-induced neuronal calcium influx and require heparan sulfate preotoglycan-mediated endocytosis to induce a neuroprotective effect. Furthermore, neuroprotection could be induced with immediate peptide treatment or treatment up to 2 to 4 hours before glutamic acid excitotoxicity or OGD, and with poly-arginine-9 (R9) when administered intravenously after stroke onset in a rat model. In contrast, the JNKI-1 peptide when fused to the (non-arginine) kFGF CPP, which does not rely on endocytosis for uptake, was not neuroprotective in the glutamic acid model; the kFGF peptide was also ineffective. Similarly, positively charged poly-lysine-10 (K10) and R9 fused to the negatively charged poly-glutamic acid-9 (E9) peptide (R9/E9) displayed minimal neuroprotection after excitotoxicity. These results indicate that peptide positive charge and arginine residues are critical for neuroprotection, and have led us to hypothesize that peptide-induced endocytic internalization of ion channels is a potential mechanism of action. The findings also question the mode of action of different neuroprotective peptides fused to arginine-rich CPPs.

Sign in / Sign up

Export Citation Format

Share Document