The Good and the Bad of Molecular Crowding for the Diffusion-Capture of Molecules in Synapses

2020 ◽  
Author(s):  
Marianne Renner
Keyword(s):  
Molecular Crowding

scholarly journals Combined Effects of Methylated Cytosine and Molecular Crowding on the Thermodynamic Stability of DNA Duplexes

2021 ◽  
Vol 22 (2) ◽  
pp. 947
Author(s):  
Mitsuki Tsuruta ◽  
Yui Sugitani ◽  
Naoki Sugimoto ◽  
Daisuke Miyoshi
Keyword(s):  
Molecular Crowding ◽  
Dna Duplexes ◽  
Crowding Effect ◽  
Backbone Flexibility ◽  
Cpg Dinucleotides ◽  
Key Factor ◽  
Dna Backbone ◽  
A Cell ◽  
Stabilization Effect ◽  
And Function

Methylated cytosine within CpG dinucleotides is a key factor for epigenetic gene regulation. It has been revealed that methylated cytosine decreases DNA backbone flexibility and increases the thermal stability of DNA. Although the molecular environment is an important factor for the structure, thermodynamics, and function of biomolecules, there are few reports on the effects of methylated cytosine under a cell-mimicking molecular environment. Here, we systematically investigated the effects of methylated cytosine on the thermodynamics of DNA duplexes under molecular crowding conditions, which is a critical difference between the molecular environment in cells and test tubes. Thermodynamic parameters quantitatively demonstrated that the methylation effect and molecular crowding effect on DNA duplexes are independent and additive, in which the degree of the stabilization is the sum of the methylation effect and molecular crowding effect. Furthermore, the effects of methylation and molecular crowding correlate with the hydration states of DNA duplexes. The stabilization effect of methylation was due to the favorable enthalpic contribution, suggesting that direct interactions of the methyl group with adjacent bases and adjacent methyl groups play a role in determining the flexibility and thermodynamics of DNA duplexes. These results are useful to predict the properties of DNA duplexes with methylation in cell-mimicking conditions.

Virus Mechanics under Molecular Crowding

2021 ◽  
Vol 125 (7) ◽  
pp. 1790-1798
Author(s):  
Cheng Zeng ◽  
Liam Scott ◽  
Andrey Malyutin ◽  
Roya Zandi ◽  
Paul Van der Schoot ◽  
...  
Keyword(s):  
Molecular Crowding

scholarly journals The CaMKII holoenzyme structure in activation-competent conformations

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Janette B. Myers ◽  
Vincent Zaegel ◽  
Steven J. Coultrap ◽  
Adam P. Miller ◽  
K. Ulrich Bayer ◽  
...  
Keyword(s):  
Molecular Crowding ◽  
Extended State ◽  
Dependent Protein Kinase ◽  
Subunit Exchange ◽  
Regulatory Processes ◽  
Predominant Form ◽  
Dependent Protein ◽  
Bona Fide ◽  
Additional Level ◽  
Compact Conformation

Abstract The Ca2+/calmodulin-dependent protein kinase II (CaMKII) assembles into large 12-meric holoenzymes, which is thought to enable regulatory processes required for synaptic plasticity underlying learning, memory and cognition. Here we used single particle electron microscopy (EM) to determine a pseudoatomic model of the CaMKIIα holoenzyme in an extended and activation-competent conformation. The holoenzyme is organized by a rigid central hub complex, while positioning of the kinase domains is highly flexible, revealing dynamic holoenzymes ranging from 15–35 nm in diameter. While most kinase domains are ordered independently, ∼20% appear to form dimers and <3% are consistent with a compact conformation. An additional level of plasticity is revealed by a small fraction of bona-fide 14-mers (<4%) that may enable subunit exchange. Biochemical and cellular FRET studies confirm that the extended state of CaMKIIα resolved by EM is the predominant form of the holoenzyme, even under molecular crowding conditions.

scholarly journals Investigating molecular crowding during cell division and hyperosmotic stress in budding yeast with FRET

2021 ◽  
pp. 75-118
Author(s):  
Sarah Lecinski ◽  
Jack W. Shepherd ◽  
Lewis Frame ◽  
Imogen Hayton ◽  
Chris MacDonald ◽  
...  
Keyword(s):  
Cell Division ◽  
Budding Yeast ◽  
Hyperosmotic Stress ◽  
Molecular Crowding

scholarly journals Thermodynamic Aspects of Homeopathy

2020 ◽  
Author(s):  
Mihael Drofenik
Keyword(s):  
Thermodynamic Model ◽  
Healthy Person ◽  
Mass Action ◽  
Molecular Crowding ◽  
Science And Art ◽  
Healthy State ◽  
The Law ◽  
Definition Of ◽  
The Individual ◽  
Necessary And Sufficient

The well-known definition of disease, which Samuel Hahnemann presented in a tentative theory for his new science and art of healing, is used as the starting point for the thermodynamic model of homeopathy. The Le Chatelier principle was applied to the biochemical equilibrium compartmentalized in the individual human cells of an ill person to explain the curing based on the re-establishment of the starting equilibrium of a healthy person when using a remedy. It is revealed that a high dilution accompanied by succession is required to release the remedies to their constituent molecular species in order to increase their activity when taking part in the biochemical equilibrium that is essential for healing. In addition, a single remedy reaction-product species, when it is in excess, as well as satisfying the kinetic equilibrium, is a necessary and sufficient condition to force the new biochemical equilibrium in the direction of the basic original equilibrium associated with a healthy state. In addition, homeopathic aggravation is considered on the basis of the Law of Mass Action and the role of the small remedy concentration in some high-profile models is revisited. The second elementary law of homeopathy, the Law of the Infinitesimals, was explained based on a kinetic model. When a remedy occurs in the human cell of a healthy person and forms a reaction product (Simillimum) that induces the finest medical symptoms of an ill person, then remedies entering the cell of the ill person will form identical Simillimum molecules and re-establish the initial equilibrium of the healthy state and cure the ill person. However, this will also induce a molecular crowding in the cells of the ill person. For kinetic reasons, this will aggravate the re-establishment of the initial equilibrium and consequently worsen or even interrupt the medical treatment. At a low remedy concentration, the molecular crowding becomes negligible while the formation of the Simillimum and the re-establishment of the initial equilibrium will take place continuously and cure the person who is ill. The final understanding of the Simillimum in the thermodynamic model was illuminated and wide-opened its duality with the ill person’s key compound.

scholarly journals Multivalent proteins rapidly and reversibly phase-separate upon osmotic cell volume change

2019 ◽  
Author(s):  
Ameya P. Jalihal ◽  
Sethuramasundaram Pitchiaya ◽  
Lanbo Xiao ◽  
Pushpinder Bawa ◽  
Xia Jiang ◽  
...  
Keyword(s):  
Phase Separation ◽  
Cell Volume ◽  
Volume Change ◽  
Mammalian Cells ◽  
Internal State ◽  
Transcription Termination ◽  
Cell Types ◽  
List Type ◽  
Molecular Crowding ◽  
Minimal Impact

SUMMARYProcessing bodies (PBs) and stress granules (SGs) are prominent examples of sub-cellular, membrane-less compartments that are observed under physiological and stress conditions, respectively. We observe that the trimeric PB protein DCP1A rapidly (within ∼10 s) phase-separates in mammalian cells during hyperosmotic stress and dissolves upon isosmotic rescue (over ∼100 s) with minimal impact on cell viability even after multiple cycles of osmotic perturbation. Strikingly, this rapid intracellular hyperosmotic phase separation (HOPS) correlates with the degree of cell volume compression, distinct from SG assembly, and is exhibited broadly by homo-multimeric (valency ≥ 2) proteins across several cell types. Notably, HOPS sequesters pre-mRNA cleavage factor components from actively transcribing genomic loci, providing a mechanism for hyperosmolarity-induced global impairment of transcription termination. Together, our data suggest that the multimeric proteome rapidly responds to changes in hydration and molecular crowding, revealing an unexpected mode of globally programmed phase separation and sequestration that adapts the cell to volume change.GRAPHICAL ABSTRACTIN BRIEFCells constantly experience osmotic variation. These external changes lead to changes in cell volume, and consequently the internal state of molecular crowding. Here, Jalihal and Pitchiaya et al. show that multimeric proteins respond rapidly to such cellular changes by undergoing rapid and reversible phase separation.HIGHLIGHTSDCP1A undergoes rapid and reversible hyperosmotic phase separation (HOPS)HOPS of DCP1A depends on its trimerization domainSelf-interacting multivalent proteins (valency ≥ 2) undergo HOPSHOPS of CPSF6 explains transcription termination defects during osmotic stress

Stabilization of Three-Way Junctions of DNA under Molecular Crowding Conditions

2009 ◽  
Vol 131 (26) ◽  
pp. 9268-9280 ◽  
Author(s):  
Sanjukta Muhuri ◽  
Kenta Mimura ◽  
Daisuke Miyoshi ◽  
Naoki Sugimoto
Keyword(s):  
Molecular Crowding
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