scholarly journals Ion counting demonstrates a high electrostatic potential of the nucleosome

2019 ◽  
Author(s):  
Magdalena Gebala ◽  
Stephanie Johnson ◽  
Geeta Narlikar ◽  
Daniel Herschlag
Keyword(s):  
Electrostatic Field ◽  
Dna Binding Proteins ◽  
Electrostatic Repulsion ◽  
Computational Studies ◽  
Histone Protein ◽  
Dna Compaction ◽  
Histone Octamer ◽  
Nucleosome Formation ◽  
And Function ◽  
Positively Charged

AbstractThe fundamental unit of chromatin is the nucleosome, which comprises of DNA wrapped around a histone protein octamer. The association of positively charged histone proteins with negatively charged DNA is intuitively thought to attenuate the electrostatic repulsion of DNA, resulting in a weakly charged nucleosome complex. 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 models 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. Further, our results show that the wrapping of DNA around a histone octamer increases the propensity of the DNA to make interactions with multivalent cations like Mg2+. These findings indicate that presentation of DNA on a nucleosome may more strongly attract positively-charged DNA binding proteins. 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.

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.

scholarly journals The Trade-off between Thermostability and Function in Designed DNA-Binding Proteins

2021 ◽  
Vol 120 (3) ◽  
pp. 19a
Author(s):  
Lauren A. Verheyden ◽  
Lily A. Schumacher ◽  
Andrew Bigler ◽  
Natali A. Gonzalez ◽  
Emily Hamlin ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Proteins ◽  
Dna Binding Proteins ◽  
Trade Off ◽  
And Function

scholarly journals DNA sliding and loop formation by E. coli SMC complex: MukBEF

2021 ◽  
Author(s):  
man zhou
Keyword(s):  
Single Molecule ◽  
Atp Hydrolysis ◽  
Dna Interaction ◽  
Loop Formation ◽  
Unknown Mechanism ◽  
E Coli ◽  
Dna Compaction ◽  
And Function ◽  
Structural Maintenance Of Chromosomes

SMC (structural maintenance of chromosomes) complexes share conserved architectures and function in chromosome maintenance via an unknown mechanism. Here we have used single-molecule techniques to study MukBEF, the SMC complex in Escherichia coli. Real-time movies show MukB alone can compact DNA and ATP inhibits DNA compaction by MukB. We observed that DNA unidirectionally slides through MukB, potentially by a ratchet mechanism, and the sliding speed depends on the elastic energy stored in the DNA. MukE, MukF and ATP binding stabilize MukB and DNA interaction, and ATP hydrolysis regulates the loading/unloading of MukBEF from DNA. Our data suggests a new model for how MukBEF organizes the bacterial chromosome in vivo; and this model will be relevant for other SMC proteins.

A positively charged tight UF membrane and its properties for removing trace metal cations via electrostatic repulsion mechanism

2019 ◽  
Vol 373 ◽  
pp. 168-175 ◽  
Author(s):  
Ming-Yong Zhou ◽  
Peng Zhang ◽  
Li-Feng Fang ◽  
Bao-Ku Zhu ◽  
Jian-Li Wang ◽  
...  
Keyword(s):  
Trace Metal ◽  
Metal Cations ◽  
Electrostatic Repulsion ◽  
Positively Charged

scholarly journals The Crosstalk between Acetylation and Phosphorylation: Emerging New Roles for HDAC Inhibitors in the Heart

2018 ◽  
Vol 20 (1) ◽  
pp. 102 ◽  
Author(s):  
Justine Habibian ◽  
Bradley Ferguson
Keyword(s):  
Gene Expression ◽  
Protein Phosphorylation ◽  
Cross Talk ◽  
Electrostatic Interactions ◽  
Regulation Of Gene Expression ◽  
Hdac Inhibitors ◽  
Protein Activity ◽  
Histone Protein ◽  
Signal Transduction Protein ◽  
And Function

Approximately five million United States (U.S.) adults are diagnosed with heart failure (HF), with eight million U.S. adults projected to suffer from HF by 2030. With five-year mortality rates following HF diagnosis approximating 50%, novel therapeutic treatments are needed for HF patients. Pre-clinical animal models of HF have highlighted histone deacetylase (HDAC) inhibitors as efficacious therapeutics that can stop and potentially reverse cardiac remodeling and dysfunction linked with HF development. HDACs remove acetyl groups from nucleosomal histones, altering DNA-histone protein electrostatic interactions in the regulation of gene expression. However, HDACs also remove acetyl groups from non-histone proteins in various tissues. Changes in histone and non-histone protein acetylation plays a key role in protein structure and function that can alter other post translational modifications (PTMs), including protein phosphorylation. Protein phosphorylation is a well described PTM that is important for cardiac signal transduction, protein activity and gene expression, yet the functional role for acetylation-phosphorylation cross-talk in the myocardium remains less clear. This review will focus on the regulation and function for acetylation-phosphorylation cross-talk in the heart, with a focus on the role for HDACs and HDAC inhibitors as regulators of acetyl-phosphorylation cross-talk in the control of cardiac function.

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.

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