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)
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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]....
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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
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TL;DR: It is argued that analysis of the DeltaH and DeltaS of ligand binding may give useful information on ligand-induced changes in membrane-bound receptor oligomers, relevant to the differing effects of agonists and antagonists.
35 citations
"Native aggregation as a cause of or..." refers background in this paper
...[42] note that the orderliness of a polypeptide chain is closely connected with protein function....
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31 citations
"Native aggregation as a cause of or..." refers background in this paper
...conclusion that denaturational protein changes appear when an egg cell is fertilized [19] and during photoreception [20]....
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Journal Article•
TL;DR: The review describes the experimental testing of the association-induction (AI) hypothesis and describes the AIH-based electronic and molecular mechanisms for the coherent assemblage of the components, for the maintenance of the living states and for the auto-cooperative transitions between the resting and active living state.
Abstract: Among the most promising scientific achievements of the 19th century was the recognition that the laws governing the dead world also govern the world of the living and that life has a physical basis called protoplasm. Regrettably, the definition of protoplasm provided then was (inescapably) incorrect, offering a (legitimate) reason for rejecting the concept of protoplasm by an overwhelming majority of later investigators, teachers and other opinion-makers. Without a recognized physical basis, Life itself also faded into the limbo of the unexplainable. However, eventually the needed relevant parts of physics and chemistry to give a more cogent definition of protoplasm became available. That then made possible the construction in the early 1960's of a unifying theory of the living cell, named the association-induction (AI) hypothesis. Historically speaking, the AI Hypothesis is the heir to the general concept of protoplasm as the physical basis of life-incorrect as the initial definition of protoplasm was notwithstanding. In the AI Hypothesis (AIH) the true or ultimate physical basis of life is not what the advocates of the protoplasm once considered as the physical basis of life. What they saw and construed as the physical basis of life is a particular kind of macroscopic protoplasm. In the AI Hypothesis, the basic unit (or physical basis) of life is microscopic protoplasm or nano-protoplasm, of which all macroscopic protoplasm is made. The AI Hypothesis also had no difficulty offering a new definition to what life is in terms of fundamental physical-chemical laws. Nano-protoplasm is defined by what it is and what it does. In greater detail, it is defined (i) by its chemical composition given in Equation 1 on p. 124; (ii) by the mutual spatial and energetic relationships among the components as illustrated diagrammatically in Figure 5 on p. 125; and (iii) by the ability of these components to exist as coherent assemblies in either one of two alternative states, the resting and active living (or dead) state as according to Equation 5 on p. 142. The review then describes the AIH-based electronic and molecular mechanisms for the coherent assemblage of the components, for the maintenance of the living states and for the auto-cooperative transitions between the resting and active (or dead) living state. Having completed the theoretical section, the review goes on to describe the experimental testing of the theory carried out in the past forty-some years (and even in time before that by authors who knew nothing of the theory.) These experimental studies fall into two broad categories. In the first category, are the experiments performed on ultra-simple models of nano-protoplasm made up from pure chemicals as prescribed in Equation 1 on p. 124. The results show that they indeed behave qualitatively like that illustrated in Figure 5 and quantitatively follow the dictates of Equation 5. In the second category of experimental testing, parallel studies were carried out on nano-protoplasm as part of living cells--in carrying out each one of the four classical functions of cell physiology: (1) solute and water distribution; (2) solute and water permeability; (3) cellular resting and action potentials; (4) cellular swelling and shrinkage. The results show that the nano-protoplasm in situ too qualitatively behave like that shown in Figure 5 and quantitatively follow the dictates of Equation 5. The review ends on a discussion section, examining how cogent do the experimental data accumulated thus far support to the AI version of the concept of nano-protoplasm as the most basic unit of life.
26 citations
Journal Article•
TL;DR: A new interpretation of the mechanism of the universal reaction is proposed, and a possible role for contractile proteins in the mechanisms of the UCR of muscle cells is presented, and the concept of cell hydrophobicity is introduced.
Abstract: My goal is to describe briefly the universal cellular reaction (UCR) to external actions and agents. This general reaction was the main subject of investigation by the scientific school of the outstanding Russian cytologist, Dmitrii Nasonov (1895-1957). The UCR consists of two phases of complex changes in cellular viscosity and turbidity, in the cell's ability to bind vital dyes, in the resting membrane potential, and in cellular resistance to harmful actions. Works from the Nasonov School have shown that these changes are based on structural-functional transformations of many cell proteins that react uniformly to actions of different physical and chemical nature. In general, these complex changes do not depend on cell type, indicating the universal and ancient nature of the UCR as well as its general biological significance. A new interpretation of the mechanism of the universal reaction is proposed in this paper, and a possible role for contractile proteins in the mechanism of the UCR of muscle cells is presented. In addition, the concept of cell hydrophobicity is introduced. Nasonov's School proposed a concept of physiological standardization that allows comparison of data obtained by different investigators and that will also be described here.
20 citations
"Native aggregation as a cause of or..." refers background in this paper
...cellular hydrophobic phase during the protoreaction [8] and the structural changes in the universal reaction of the living cell [1]....
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...An example of this is the universal reaction of the living cell [8]....
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...It is of primary importance that the same changes also occur in the cell during its transition into the active state: muscle contraction, action potential, enhancement of secretory activity (for details, see [8])....
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...Other parameters (see [8] for review) were also studied....
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...Only one explanation for this is possible: the volume of the hydrophobic phase in the cell increases explosively [8]....
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TL;DR: Some proteins do not fold fully until they meet their functional partners, but folding in concert with binding allows an efficient stepwise search for the proper structure within the final complex.
Abstract: Some proteins do not fold fully until they meet their functional partners. Folding in concert with binding allows an efficient stepwise search for the proper structure within the final complex.
18 citations