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Yutaka Kuroda 《Biophysical reviews》2022,14(6):1495
Amorphous protein aggregates are oligomers that lack specific, high-order structures. Soluble amorphous aggregates are smaller than ~1 µm. Despite their lack of high-order structure, amorphous protein aggregates exhibit specific biophysical properties such as reversibility of formation, density, conformation, and biochemical stability. Our mutational analysis using a Solubility Controlling Peptide (SCP) tag strongly suggests that amorphous aggregation of small globular proteins can significantly increase in vivo immune response and that the magnitude of enhanced immune responses depends on the aggregates’ biophysical and biochemical properties. We propose that SCP tags might help develop subunit (protein) adjuvant-free (immunostimulant-free) vaccines by controlling the aggregation propensity of target proteins. 相似文献
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Methods for engineering proteins that contain non-canonical amino acids have advanced rapidly in the past few years. Novel amino acids can be introduced into recombinant proteins in either a residue-specific or site-specific fashion. The methods are complementary: residue-specific incorporation allows engineering of the overall physical and chemical behavior of proteins and protein-like macromolecules, whereas site-specific methods allow mechanistic questions to be probed in atomistic detail. Challenges remain in the engineering of the translational apparatus and in the design of schemes that can be used to encode both canonical and non-canonical amino acids. 相似文献
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M F Guly? 《Ukrainski? biokhimicheski? zhurnal》1985,57(5):6-22
The paper embraces data available in literature and the results of the author's investigations which show synergism and antagonism interrelations between certain amino acids in the processes of transmembrane transport, amino acylation of transfer RNA and incorporation into protein. These interrelations may lead to activation and inhibition of the protein biosynthesis. It is established that an excess of any amino acid created with its administration into the organism induces the inhibition of biosynthesis and activity of the corresponding aminoacyl-tRNA-synthetase (ARSase), while deficiency of an amino acid intensifies the biosynthesis of the corresponding ARSase. Homogeneous crystalline proteins, such as aldolase of rabbit skeletal muscles, collagen I of rat skin, globin of chicken blood and others, are used as an example to show that as a result of feeding of the amino acid excess to animals, especially against a background of protein deficiency, the biosynthesis intensity changes and proteins with other primary structure and properties are synthetized. This testifies to that amino acids being substrates in the protein biosynthesis are regulators in this process. It is established that the biosynthesis of proteins with other primary structure under conditions of complete fasting, protein deprivation, feeding of an excess of certain amino acids to animals against a background of protein deficiency, atherosclerosis and other extremal states of the organism is not a result of erroneous incorporation of amino acids but is the process of regular, specific and stable character for each state and may be predicted. The biosynthesis of the protein with other primary structure under the effect of extremal conditions is caused, apparently, by capability to the changes of the proteinsynthetizing system. 相似文献
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Mizuguchi M Hayashi A Takeuchi M Dobashi M Mori Y Shinoda H Aizawa T Demura M Kawano K 《Proteins》2008,72(1):261-269
Senile systemic amyloidosis (SSA) is caused by amyloid deposits of wild-type transthyretin in various organs. Amyloid deposits from SSA contain large amounts of the C-terminal fragments starting near amino acid residue 50 as well as full-length transthyretin. Although a number of previous studies suggest the importance of the C-terminal fragments in the pathogenesis of SSA, little is known about the structure and aggregation properties of the C-terminal fragments of transthyretin. To understand the role of C-terminal fragments in SSA, we examined the effects of the truncation of the N-terminal portions on the structure and aggregation properties of wild-type transthyretin. The deletion mutant lacking 50 N-terminal residues was largely unfolded in terms of secondary and tertiary structure, leading to self-assembly into spherical aggregations under nearly physiological conditions. By contrast, the deletion mutant lacking 37 N-terminal residues did not have a strong tendency to aggregate, although it also adopted a largely unfolded conformation. These results suggest that global unfolding of transthyretin by proteolysis near amino acid residue 50 is an important step of self-assembly into aggregations in SSA. 相似文献
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Rational design of solution additives for the prevention of protein aggregation 总被引:3,自引:0,他引:3
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We have developed a statistical-mechanical model of the effect of solution additives on protein association reactions. This model incorporates solvent radial distribution functions obtained from all-atom molecular dynamics simulations of particular proteins into simple models of protein interactions. In this way, the effects of additives can be computed along the entire association/dissociation reaction coordinate. We used the model to test our hypothesis that a class of large solution additives, which we term "neutral crowders," can slow protein association and dissociation by being preferentially excluded from protein-protein encounter complexes, in a manner analogous to osmotic stress. The magnitude of this proposed "gap effect" was probed for two simple model systems: the association of two spheres and the association of two planes. Our results suggest that for a protein of 20 A radius, an 8 A additive can increase the free energy barrier for association and dissociation by as much as 3-6 kcal/mol. Because the proposed gap effect is present only for reactions involving multiple molecules, it can be exploited to develop novel additives that affect protein association reactions although having little or no effect on unimolecular reactions such as protein folding. This idea has many potential applications in areas such as the stabilization of proteins against aggregation during folding and in pharmaceutical formulations. 相似文献
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Investigation of protein quality--ileal recovery of amino acids 总被引:3,自引:0,他引:3
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A comparison is made of the N- and C-terminal amino acids from 96 published protein sequences, 26 from prokaryotes, 70 from eukaryotes. The observed frequencies of the N-terminal amino acids methionine, alanine and serine in prokaryotes, and alanine and serine in eukaryotes are significantly higher than expected for a random arrangement of amino acids. At the C-terminal end, the observed frequencies of lysine, asparagine and glutamine in prokaryotes and phenylalanine, asparagine and glutamine in eukaryotes exceed random expectation. These results could be explained by specific proteolytic cleavage during protein synthesis. 相似文献
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The present paper is an attempt to study the mechanism of ethanol induced aggregation of chicken egg albumin and to stabilize the protein against ethanol induced aggregation. The protein aggregation was determined by monitoring the light scattering of protein aggregates spectrophotometrically. The protein undergoes certain structural changes in water-ethanol solution and the degree of aggregation was found to be linearly depending upon the concentration of alcohol used. The intrinsic fluorescence study showed a large blue shift in the λ(max) (16 nm) in the presence of 50% ethanol. The ANS fluorescence intensity was found to be gradually increasing with increasing concentration of ethanol. This indicates an increase in the hydrophobic cluster on the protein surface and as a result the hydrophobic interaction is the major driving force for the aggregate formation. Addition of sucrose significantly reduced the ethanol-induced protein aggregation. In presence of 50% sucrose the ethanol the aggregation was reduced to 5%. The study reveals that addition of sucrose brings out changes in the solvent distribution and prevents the structural changes in protein which lead the aggregation. 相似文献
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Gut homeostasis plays a major role in health and may be regulated by quantitative and qualitative food intake. In the intestinal mucosa, an intense renewal of proteins occurs, at approximately 50 % per day in humans. In some pathophysiological conditions, protein turnover is altered and may contribute to intestinal or systemic diseases. Amino acids are key effectors of gut protein turnover, both as constituents of proteins and as regulatory molecules limiting intestinal injury and maintaining intestinal functions. Many studies have focused on two amino acids: glutamine, known as the preferential substrate of rapidly dividing cells, and arginine, another conditionally essential amino acid. The effects of glutamine and arginine on protein synthesis appear to be model and condition dependent, as are the involved signaling pathways. The regulation of gut protein degradation by amino acids has been minimally documented until now. This review will examine recent data, helping to better understand how amino acids regulate intestinal protein metabolism, and will explore perspectives for future studies. 相似文献
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Three specific growth rates, 0.23, 0.45 and 0.51 h–1, were used to cultivate Corynebacterium glutamicum in a pH-auxostat. The specific formation rates of most amino acids increased by raising the specific growth rates. The highest specific growth rate, 0.51 h–1, favors the production of LEU; whereas the highest production yield for ALA and GLU were at = 0.23 h–1. A correlation among specific growth rates, glucose consumption rate, and production yields of amino acids was obtained. 相似文献
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M. H. De Jong C. Van Der Drift C. Stumm J. J. A. Arends 《Archives of microbiology》1977,113(1-2):153-158
Constant levels of amino acids enhanced the velocity of Bacillus subtilis 60015 cells about 2-fold and stimulated the response in motility assays. The stimulation of velocity did not occur via the receptors for chemotaxis. Cysteine and methionine, general inhibitors of chemotaxis, both completely inhibited the smooth response in a temporal gradient of attractant. After methionine starvation B. subtilis 60015 showed no measurable response in a temporal gradient of attractant, this in contrast to the effect observed with some other bacteria. Addition of methionine to starved cells restored the response toward attractant. Revertants of B. subtilis 60015 for methionine requirement could not be starved and showed a normal behavior toward temporal gradients of attractant.Abbreviation O.D.600
optical density measured at 600 nm 相似文献