Native aggregation as a cause of origin of temporary cellular structures needed for all forms of cellular activity, signaling and transformations
TL;DR: According to the hypothesis explored in this paper, native aggregation is genetically controlled (programmed) reversible aggregation that occurs when interacting proteins form new temporary structures through highly specific interactions.
Abstract: According to the hypothesis explored in this paper, native aggregation is genetically controlled (programmed) reversible aggregation that occurs when interacting proteins form new temporary structures through highly specific interactions. It is assumed that Anfinsen's dogma may be extended to protein aggregation: composition and amino acid sequence determine not only the secondary and tertiary structure of single protein, but also the structure of protein aggregates (associates). Cell function is considered as a transition between two states (two states model), the resting state and state of activity (this applies to the cell as a whole and to its individual structures). In the resting state, the key proteins are found in the following inactive forms: natively unfolded and globular. When the cell is activated, secondary structures appear in natively unfolded proteins (including unfolded regions in other proteins), and globular proteins begin to melt and their secondary structures become available for interaction with the secondary structures of other proteins. These temporary secondary structures provide a means for highly specific interactions between proteins. As a result, native aggregation creates temporary structures necessary for cell activity. "One of the principal objects of theoretical research in any department of knowledge is to find the point of view from which the subject appears in its greatest simplicity." Josiah Willard Gibbs (1839-1903)
Citations
More filters
TL;DR: Low molecular-weight metabolites (LMWMs) as discussed by the authors comprise primary or central and a plethora of intermediary or secondary metabolites, all of which are characterized by a molecular weight below 900 Dalton.
Abstract: Low-molecular-weight metabolites (LMWMs) comprise primary or central and a plethora of intermediary or secondary metabolites, all of which are characterized by a molecular weight below 900 Dalton. The latter are especially prominent in sessile higher organisms, such as plants, corals, sponges and fungi, but are produced by all types of microbial organisms too. Common to all of these carbon molecules are oxygen, nitrogen and, to a lesser extent, sulfur, as heteroatoms. The latter can contribute as electron donators or acceptors to cellular redox chemistry and define the potential of the molecule to enter charge-transfer complexes. Furthermore, they allow LMWMs to serve as organic ligands in coordination complexes of various inorganic metals as central atoms. Especially the transition metals Fe, Cu and Mn can catalyze one electron reduction of molecular oxygen, which results in formation of free radical species and reactive follow-up reaction products. As antioxidants LMWMs can scavenge free radicals. Depending on the chemical environment, the same LMWMs can act as pro-oxidants by reducing molecular oxygen. The cellular regulation of redox homeostasis, a balance between oxidation and reduction, is still far from being understood. Charge-transfer and coordination complex formation with metals shapes LMWMs into gel-like matrices in the cytosol. The quasi-polymer structure is lost usually during the isolation procedure. In the gel state, LMWMs possess semiconductor properties. Also proteins and membranes are semiconductors. Together they can represent biotransistor components that can be part of a chemoelectrical signaling system that coordinates systems chemistry by initiating cell differentiation or tissue homeostasis, the activated and the resting cell state, when it is required. This concept is not new and dates back to Albert Szent-Gyorgyi.
30 citations
TL;DR: The evidence is given that the first protocells may have been formed on the basis of intrinsically disordered peptides, and available data on the similarity of the physical properties of cell models and living cells allow the Virchow's postulate to be rephrase as follows.
Abstract: Cell theory, as formulated by Theodor Schwann in 1839, introduced the idea that the cell is the main structural unit of living nature. Later, in solving the problem of cell multiplication, Rudolf Virchow expanded the cell theory with a postulate: all cells only arise from pre-existing cells. But what did the very first cell arise from? This paper proposes extending the Virchow's law by the assumption that between the nonliving protocell and the first living cell the continuity of fundamental physical properties (the principle of invariance of physical properties) is preserved. The protocell is understood here as a cell-shaped physical system on the basis of the self-organized biologically significant prebiotic macromolecules, primarily peptides, having a potential to transform into the living cell. Biophase is considered as the physical basis of the membraneless protocell, the internal environment of which is separated from the external environment due to the phase of adsorbed water. The evidence is given that the first protocells may have been formed on the basis of intrinsically disordered peptides. Data on the similarity of the physical properties of living cells and the following model systems are given: protein and artificial polymer solutions, coacervate droplets, and ion-exchange resin granules. Available data on the similarity of the physical properties of cell models and living cells allow us to rephrase the Virchow's postulate as follows: the physical properties of a living cell could only arise from pre-existing physical properties of the protocell.
25 citations
TL;DR: The ATP effect on protein aggregation was ambiguous: ATP alone had no effect on the protein’s thermal stability but it facilitated protein‘s destabilization in the presence of nitric oxide.
Abstract: Background and objective
Regulating protein function in the cell by small molecules, provide a rapid, reversible and tunable tool of metabolic control. However, due to its complexity the issue is poorly studied so far. The effects of small solutes on protein behavior can be studied by examining changes of protein secondary structure, in its hydrodynamic radius as well as its thermal aggregation. The study aim was to investigate effects of adenosine-5’-triphosphate (ATP), spermine NONOate (NO donor) as well as sodium/potassium ions on thermal aggregation of albumin and hemoglobin. To follow aggregation of the proteins, their diffusion coefficients were measured by quasi-elastic light scattering (QELS) at constant pH (7.4) in the presence of solutes over a temperature range from 25°C to 80°C.
18 citations
Cites background from "Native aggregation as a cause of or..."
...Discussion Protein aggregation plays an important role in the cellular biology and in many applications of protein science and medical engineering [28]....
[...]
Journal Article•
17 citations
TL;DR: Ling's theory is a complete quantitative theory with corroborated equations for solute distribution, transport, cell potentials and osmotic behaviour and describing the cell's energy cycle and IDP's are involved in all this.
Abstract: The example of gelatine shows that extended proteins behave quite differently than globular ones: with water they form a gel. Historically the colloid view of protoplasm was discredited in favour of membrane-(pump)-theory (MPT), but unjustified. In his association-induction hypothesis Ling demonstrates that MPT is full of contradictions and that the colloid view has to be re-considered. In that case IDP's play a crucial role in this. What Ling calls the ‘living state’ consists of the unitary protoplasmic structure from which it was experimentally demonstrated that it can survive and keep Na+ and K+ concentrations without a delineating membrane. It consists of unfolded polypeptide chains whereby the repetitive backbone peptide groups orient and polarise many layers of water, in which Na+ and other solutes have reduced solubility and whereby the polypeptide β- and ϒ-carboxyl-groups adsorb K+. This ‘associated’ state is the resting state: a coherent high-energy low-entropy meta-stable state. It can be kept by adsorbed ATP (NTP) eventually for years without consumption of ATP as demonstrated by Clegg on Artemia embryo's. Stimuli can transform this state into a lower-energy higher-entropy action state with dissociation of ADP and Pi and newly synthesised ATP can reinstall it. Rest-to-action and action-to-rest were shown to be real phase-shifts. Ling's theory is a complete quantitative theory with corroborated equations for solute distribution, transport, cell potentials and osmotic behaviour and describing the cell's energy cycle. IDP's are involved in all this. The new view on IDP's leads to new insights on the origin of life.
17 citations
References
More filters
TL;DR: Small heat-shock proteins are a widespread and diverse class of molecular chaperones that maintain protein homeostasis by binding proteins in non-native conformations, thereby preventing substrate aggregation.
Abstract: Small heat-shock proteins (sHsps) are a widespread and diverse class of molecular chaperones. Recent evidence suggests that they maintain protein homeostasis by binding proteins in non-native conformations, thereby preventing substrate aggregation. Some members of the sHsp family are inactive or only partially active under physiological conditions, and transition toward the active state is induced by specific triggers, such as elevated temperature. Release of substrate proteins bound to sHsps requires cooperation with ATP-dependent chaperones, suggesting that sHsps create a reservoir of non-native proteins for subsequent refolding.
781 citations
741 citations
"Native aggregation as a cause of or..." refers background in this paper
...Fulton [13], a convinced Porter devotee, moved even further: she put forward a point of view that "the cytoplasm is so compact that it is only occasionally more open than a crystal"....
[...]
TL;DR: Necrosis appears to be a specific form of execution phase of programmed cell death, and there are several examples of necrosis during embryogenesis, a normal tissue renewal, and immune response.
704 citations
"Native aggregation as a cause of or..." refers background in this paper
...If we deny the existence of specific mechanisms in cell protein aggregation, we will not be able to understand why cell stress initiates such processes as proliferation, differentiation, senescence, apoptosis, necrosis, or mitotic cell death [21]....
[...]
TL;DR: Overall, intrinsic disorder appears to be a common, with eucaryotes perhaps having a higher percentage of native disorder than archaea or bacteria, and bacteria and archaea in various archaea ranged from 2 to 11%, plus an apparently anomalous 18% in bacteria.
Abstract: Intrinsic protein disorder refers to segments or to whole proteins that fail to fold completely on their own. Here we predicted disorder on protein sequences from 34 genomes, including 22 bacteria, 7 archaea, and 5 eucaryotes. Predicted disordered segments > or = 50, > or = 40, and > or = 30 in length were determined as well as proteins estimated to be wholly disordered. The five eucaryotes were separated from bacteria and archaea by having the highest percentages of sequences predicted to have disordered segments > or = 50 in length: from 25% for Plasmodium to 41% for Drosophila. Estimates of wholly disordered proteins in the bacteria ranged from 1% to 8%, averaging to 3 +/- 2%, estimates in various archaea ranged from 2 to 11%, plus an apparently anomalous 18%, averaging to 7 +/- 5% that drops to 5 +/- 3% if the high value is discarded. Estimates in the 5 eucarya ranged from 3 to 17%. The putative wholly disordered proteins were often ribosomal proteins, but in addition about equal numbers were of known and unknown function. Overall, intrinsic disorder appears to be a common, with eucaryotes perhaps having a higher percentage of native disorder than archaea or bacteria.
642 citations
"Native aggregation as a cause of or..." refers background in this paper
...Subsequently it was found that more than 35-51% of eukaryotic proteins had unfolded regions longer than 50 consecutive amino acid residues, which is significantly higher than in prokaryotes [34,35]....
[...]
TL;DR: Water can generate small active clusters and macroscopic assemblies, which can both transmit information on different scales and allow water to execute an intricate three-dimensional 'ballet' while retaining complex order and enduring effects.
Abstract: Liquid water is a highly versatile material. Although it is formed from the tiniest of molecules, it can shape and control biomolecules. The hydrogen-bonding properties of water are crucial to this versatility, as they allow water to execute an intricate three-dimensional 'ballet', exchanging partners while retaining complex order and enduring effects. Water can generate small active clusters and macroscopic assemblies, which can both transmit information on different scales.
566 citations
"Native aggregation as a cause of or..." refers background in this paper
...The content of bound water in cancer cells is known to be lower than in precursor cells [49]....
[...]