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Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent advances have significantly increased the time and spectroscopic resolution of protein folding experiments. We can now study the timescale and nature of polypeptide collapse, and how this correlates with secondary and tertiary structure formation. Studies on ultrafast folding proteins and peptides provide experimental benchmarks on a timescale that overlaps directly with that of molecular dynamics simulations. This makes possible direct tests of both simulations and current models of protein folding.
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PMID:Early events in protein folding. 1258 63

A simple Monte Carlo method was used to generate ensembles of simulated polypeptide conformations that are restricted only by steric repulsion. The models used for these simulations were based on the sequences of four real proteins, ranging in size from 26 to 268 amino acid residues, and included all non-hydrogen atoms. Two sets of calculations were performed, one that included only intra-residue steric repulsion terms and those between adjacent residues, and one that included repulsion terms between all possible atom pairs, so as to explicitly account for the excluded volume effect. Excluded volume was found to increase the average radius of gyration of the chains by 20-40%, with the expansion factor increasing with chain length. Contrary to recent suggestions, however, the excluded volume effect did not greatly restrict the distribution of dihedral angles or favor native-like topologies. The average dimensions of the ensembles calculated with excluded volume were consistent with those measured experimentally for unfolded proteins of similar sizes under denaturing conditions, without introducing any adjustable scaling factor. The simulations also reproduced experimentally determined effective concentrations for the formation of disulfide bonds in reduced and unfolded proteins. The statistically generated ensembles included significant numbers of conformations that were nearly as compact as the corresponding native proteins, as well as many that were as accessible to solvent as a fully extended chain. On the other hand, conformations with as much buried surface area as the native proteins were very rare, as were highly extended conformations. These results suggest that the overall properties of unfolded proteins can be usefully described by a random coil model and that an unfolded polypeptide can undergo significant collapse while losing only a relatively small fraction of its conformational entropy.
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PMID:Computational simulation of the statistical properties of unfolded proteins. 1259 69

Anthrax, a disease of mammals (including humans), is caused by a spore-forming Gram-positive bacilli called Bacillus anthracis. Anthrax is one of the oldest threats to humanity, and remains endemic in animals in many parts of the world. The incidence of anthrax has decreased in developed countries, but it remains a considerable health problem in developing countries. The disease is transmitted to humans by contact with sick animals or their products, such as wool, skin, meat etc. Capsular polypeptide and anthrax toxin are the principal virulence factors of B. anthracis. Anthrax toxin consists of three proteins called protective antigen, edema factor, and lethal factor, each of which is nontoxic but acts synergistically. Human anthrax has three major clinical forms: cutaneous, inhalational, and gastrointestinal. The diagnosis is easily established in cutaneous cases, characterized by black eschar. Severe intoxication and collapse during the course of bronchopneumonia or hemorrhagic enteritis should prompt suspicion of anthrax. Treatment with antibiotics is mandatory. If untreated, anthrax in all forms can lead to septicemia and death. Recently, considerable attention has been focused on the potential for B. anthracis to be used in acts of biological terrorism. The ease of laboratory production and its dissemination via aerosol led to its adoption by terrorists, as shown by recent events in the USA. A good knowledge of anthrax, its epidemiology, pathogenesis, clinical forms and potential as a biological weapon is essential for timely prevention and treatment. This review summarizes the current knowledge on anthrax.
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PMID:Anthrax--an overview. 1458 93

The folding reaction of acid-unfolded cytochrome c in the presence of various amounts of KCl was investigated with Trp fluorescence and resonance Raman spectroscopies. It was found that the too-early-too-much polypeptide chain collapse induced by KCl yields some stable folding intermediates, which need to overcome a higher energy barrier to fold into their native conformation. We propose that the charge distribution on the polypeptide chain is part of the folding codon encoded in the linear amino acid sequence. The charge screening effect introduced by KCl alters the shape of the energy landscape by raising the slope of the upper rim and introduces a rugged energy surface toward the bottom of the folding funnel.
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PMID:Modulation of the folding energy landscape of cytochrome C with salt. 1550 49

The earliest folding events in single-tryptophan mutants of RNase A were investigated by fluorescence measurements by using a combination of stopped-flow and continuous-flow mixing experiments covering the time range from 70 micros to 10 s. An ultrarapid double-jump mixing protocol was used to study refolding from an unfolded ensemble containing only native proline isomers. The continuous-flow measurements revealed a series of kinetic events on the submillisecond time scale that account for the burst-phase signal observed in previous stopped-flow experiments. An initial increase in fluorescence within the 70-micros dead time of the continuous-flow experiment is consistent with a relatively nonspecific collapse of the polypeptide chain whereas a subsequent decrease in fluorescence with a time constant of approximately 80 micros is indicative of a more specific structural event. These rapid conformational changes are not observed if RNase A is allowed to equilibrate under denaturing conditions, resulting in formation of nonnative proline isomers. Thus, contrary to previous expectations, the isomerization state of proline peptide bonds can have a major impact on the structural events during early stages of folding.
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PMID:Ultrarapid mixing experiments shed new light on the characteristics of the initial conformational ensemble during the folding of ribonuclease A. 1557 90

The 26S proteasome plays essential roles in cell cycle progression in various types of cell. We previously reported that the inhibition of 26S proteasome activities by a proteasome inhibitor, MG-132, exclusively caused cell cycle arrest in synchronized tobacco BY-2 cells. Here we report a further observation of 26S proteasome involvement during M/G1 transition utilizing a transgenetic BY-2 cell line that stably expresses a GFP-alpha-tubulin fusion protein (BY-GT16). Interestingly, MG-132 treatment caused the arrest of cell cycle progression prior to entering the G1 phase. Indeed, phragmoplast-like structures were formed and cortical microtubules were not organized after the collapse of the original phragmoplasts. Additionally, actin microfilaments showed irregular rearrangements when further incubated with MG-132 and as the phragmoplast-like structures developed. Since these phragmoplast-like structures had a similar configuration and ability to form cell plates to that of the original phragmoplasts, we designated these phragmoplast-like structures as extra phragmoplasts. Furthermore, we showed that a tobacco kinesin-related polypeptide of 125 kDa (TKRP125) localized in the extra phragmoplasts and that its protein level remained unchanged during MG-132 treatment. We propose that TKRP125 might be one of the possible targets of the ubiquitin-proteasome degradation pathway during M/G1 transition.
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PMID:Inhibition of proteasome by MG-132 treatment causes extra phragmoplast formation and cortical microtubule disorganization during M/G1 transition in synchronized tobacco cells. 1557 38

We investigated the effect of the carbohydrate chain and two phosphate moieties on heat-induced aggregation of hen ovalbumin. The dephosphorylated form of ovalbumin was obtained by treating the original protein with acid phosphatase. The single carbohydrate chain was removed by digestion of heat-denatured ovalbumin with glycopeptidase F, and the resulting polypeptide without this carbohydrate chain was correctly refolded to acquire protease-resistance. Thermal unfolding can be approximated by a mechanism involving a two-state transition between the folded and unfolded states with a midpoint temperature of 76 degrees C for the original form, of 74 degrees C for the dephosphorylated form, and of 71 degrees C for the carbohydrate-free form. The conformational stability of the original form was higher than that of the carbohydrate-free form. When the three forms of ovalbumin were heated to 80 degrees C and then cooled rapidly in an ice bath, the polypeptide chains were compactly collapsed to metastable intermediates with secondary structures whose properties were indistinguishable. Upon incubation at 60 degrees C, renaturation was possible for a large portion of the intermediates of the original form, but for only a small portion of those of the carbohydrate-free form. Light scattering experiments showed that in the presence of sulfate anions, the intermediates of the carbohydrate-free form aggregated to a greater extent than did those of the original form. The intermediates of the carbohydrate-free form bound to the chaperonin GroEL with about 10-fold higher affinity than those of the original form. It follows that the carbohydrate chain and the two phosphate moieties do not affect hydrophobic collapse in the kinetic refolding of hen ovalbumin but play an important role in the slow rearrangement. They block the off-pathway reaction that competes with correct refolding by effectively decreasing surface hydrophobicity.
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PMID:Role of the carbohydrate chain and two phosphate moieties in the heat-induced aggregation of hen ovalbumin. 1561 16

Local hydrophobic collapse of the polypeptide chain and transient long-range interactions in unfolded states of apomyoglobin appear to occur in regions of the amino acid sequence which, upon folding, bury an above-average area of hydrophobic surface. To explore the role of these interactions in protein folding, we prepared and characterized apomyoglobins with compensating point mutations designed to change the average buried surface area in local regions of the sequence, while conserving as much as possible the constitution of the hydrophobic core. The behavior of the mutants in quench-flow experiments to determine the folding pathway was exactly as predicted by the changes in the buried surface area parameter calculated from the amino acid sequence. In addition, spin label experiments with acid-unfolded mutant apomyoglobin showed that the transient long-range contacts that occur in the wild-type protein are abolished in the mutant, while new contacts are observed between areas that now have above-average buried surface area. We conclude that specific groupings of amino acid side-chains, which can be predicted from the sequence, are responsible for early hydrophobic interactions in the first phase of folding in apomyoglobin, and that these early interactions determine the subsequent course of the folding process.
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PMID:Sequence determinants of a protein folding pathway. 1600 92

Elastin-like polypeptides are biopolymers composed of the pentapeptide repeat Val-Pro-Gly-Xaa-Gly. Elastin-like polypeptides are soluble in aqueous solution below their transition temperature, but they hydrophobically collapse and aggregate when the temperature is raised above the transition temperature. Previous studies have suggested that the aggregation of these polypeptides in response to externally applied hyperthermia may be exploited in the use of elastin-like polypeptide for thermally targeted drug delivery. This work shows the application of elastin-like polypeptide as a delivery vehicle for a short peptide that can inhibit the transcriptional function of a specific oncogene. The coding sequence for elastin-like polypeptide was modified by the addition of the membrane translocating sequence penetratin and a peptide derived from helix 1 of the helix-loop-helix region of c-Myc (H1-S6A,F8A), known to inhibit c-Myc transcriptional function. The designed polypeptide (Pen-ELP-H1) was then expressed and purified from Escherichia coli. Cellular uptake of Pen-ELP-H1 is enhanced by both the penetratin sequence and by the hyperthermia-induced phase transition as shown by flow cytometry studies. Using immunofluorescence and reverse transcription-PCR, we show that Pen-ELP-H1 is able to disrupt the nuclear localization of c-Myc and inhibit transcriptional activation by c-Myc. Cell proliferation studies showed that Pen-ELP-H1 inhibits growth of MCF-7 cells. Furthermore, the use of hyperthermia increased the antiproliferative effect of a thermally responsive Pen-ELP-H1 approximately 2-fold compared with a nonthermally responsive control polypeptide. These studies show that genetically engineered elastin-like polypeptide carriers may provide a new way to thermally target specific oncogene inhibitors to solid tumors.
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PMID:Application of thermally responsive polypeptides directed against c-Myc transcriptional function for cancer therapy. 1602 Jun 65

Protein engineering studies suggest that the transition state for the folding of ubiquitin is highly polarised towards the N-terminal part of the sequence and involves a nucleus of residues within the beta-hairpin (residues 1-17) and main alpha-helix (residues 23-34). In contrast, the observation of small phi-values for residues in the C-terminal portion of the sequence (residues 35-76), coupled with a folding topology that results in a much higher contact order, suggests that fast folding of ubiquitin is dependent upon configurational flexibility in the C-terminal part of the polypeptide chain to ensure passage down a relatively smooth folding funnel to the native state. We show that the introduction of a small mini-hairpin motif as an extension of the native 43-50 hairpin stabilises local interactions in the C-terminal part of the sequence, resulting largely in a deceleration of the unfolding kinetics without perturbing the apparent two-state folding mechanism. However, a single-point Leu-->Phe substitution within the engineered hairpin sequence leads to the premature collapse of the denatured ensemble through the stabilisation of non-native interactions and the population of a compact intermediate. Non-linear effects in the kinetic data at low concentrations of denaturant suggest that the collapsed state, which is further stabilised in the presence of cosmotropic salts, may subsequently fold directly to the native state through a "triangular" reaction scheme involving internal rearrangement rather than unfolding and refolding.
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PMID:Engineering stabilising beta-sheet interactions into a conformationally flexible region of the folding transition state of ubiquitin. 1616 58


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