SEARCH · PubMed Health

Results for “Structural changes”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,153 records · Page 64Linked to original sources

PubMed2005

Structural changes of beta-lactoglobulin during thermal unfolding and refolding--an FT-IR and circular dichroism study.

We have quantitatively characterized by FT-IR spectroscopy the contents of secondary structure of beta-lactoglobulin during thermal unfolding and subsequent refolding. Our data clearly indicate that considerable amount of secondary structure, particularly beta-sheet, still remained intact even at 90 degrees C. Noticeable changes in secondary structure of beta-lactoglobulin were observed only above 70 degrees C. The refolded protein regained, within limits of experimental error, all of the secondary structure lost during thermal unfolding. The data also indicate that the refolding mechanism operating at pH 7.0 and 2.0 are the same. Identical secondary structure of native and refolded beta-lactoglobulin was also indicated by far-UV circular dichroic spectra of the two forms of protein. Near UV circular dichroic spectra of the same two forms showed considerable differences indicating less tertiary structure of refolded beta-lactoglobulin. The combined CD and FT-IR data indicated that refolded form of beta-lactoglobulin could be characterized as a molten globule state as it had native-like secondary structure and compromised tertiary structure.

Circular Dichroism↗

PubMed1998

Structural changes associated with the coupling of ATP hydrolysis and cation transport by the Na pump.

Most of the residues associated with cation coordination seem to reside within transmembrane segments of the alpha-subunit of the Na,K-ATPase, whereas amino acids which appear to be involved in the coordination of ATP are found in the major cytoplasmic loop between transmembrane segments M4 and M5 (see Lingrel & Kuntzweiler, 1994; Lutsenko & Kaplan, 1995). The coupling of the two functions of cation transport and ATP hydrolysis involved in the active transport of Na and K ions must involve interactions between these two structural units. This paper summarizes recent experimental results and conclusions of studies on the renal Na,K-ATPase which have employed controlled proteolysis in the presence of physiological ligands, chemical modification with a range of reagents and a variety of functional assays. The data provide evidence for movements between specific transmembrane segments associated with cation-binding conformations and coupled changes which take place in the ATP binding domain. The binding of different cations in the cation-binding domain is sensed in the ATP binding domain and manifested as a change in reactivity. This occurs at amino acid residues which are widely spaced in primary structure. It is apparent that structural changes are transmitted through much of the ATP-binding domain as a consequence of the occupancy of the cation-binding domain. We also provide evidence that both the number and identity of cations bound are also sensed in the ATP-binding domain.

Adenosine Triphosphate↗

PubMed1988

A study on the quaternary structure change of hemoglobin in the ligation process.

In order to inquire into the molecular mechanism underlying the cooperative ligand binding to hemoglobin (Hb), conformational interaction at the interfaces between subunits are investigated on the basis of the atomic coordinates of human deoxy and human carbonmonoxy Hbs. Hypothetical intermediate structures are used, each of which is obtained from the procedure where one or more subunits in deoxy Hb are replaced by the corresponding CO-liganded subunits in carbonmonoxy Hb using the method of superimposition of two sets of atomic coordinates. When either alpha or beta subunit is substituted with the corresponding subunit in carbonmonoxy Hb, serious steric hindrances are produced between alpha 1FG4(92)Arg and beta 2C3(37)Trp or between alpha 1C6(41)Thr and beta 2FG4(97)His, all of which belong to the allosteric core affected directly by ligand binding. These steric hindrances become more serious when both alpha 1(alpha 2) and beta 2(beta 1) subunits are substituted. Therefore the change in the relative distance between iron atom and porphyrin by ligation results in strain in the C-terminal residues as an effect of the steric hindrance between the FG and C segments. However, no steric hindrance can be seen between subunits when the subunits in carbonmonoxy Hb are substituted with the corresponding subunits in deoxy Hb. The nature of the quaternary structural change from liganded to deoxy Hb seems to be different from that from deoxy to liganded Hb.

Calorimetry↗

PubMed1972

Coboglobins: heterotropic linkage and the existence of a quaternary structure change upon oxygenation of cobaltohemoglobin.

Cobaltohemoglobin prepared from horse hemoglobin retains the full heterotropic linkage properties of the normal iron hemoglobin, including both the Bohr and phosphate effects. From this result, and the known connection between heterotropic linkage properties and hemoglobin conformational change, it is concluded that cobaltohemoglobin undergoes a quaternary structure transition upon oxygenation. Thus, the stereochemical changes that occur upon oxygen binding to cobalt, as well as to iron, must be compatible with the mechanism triggering such a transition.

Animals↗

PubMed1995

Do structural changes of T cell receptor complex occur in tumor-bearing state?

T cells in tumor-bearing mice and cancer patients were recently shown to be devoid of CD3-zeta chain, a signal-transducing invariant chain in T cell receptor (TCR) complex, and p56lck tyrosine kinase. In the present study, we investigated the structure and function of TCR complex in T cells from BALB/c mice bearing CSA1M fibrosarcoma. The expressions of TCR chains and p56lck in a T cell-enriched population from spleen were analyzed. Almost complete loss of CD3-zeta and p56lck was observed in the preparation from tumor-bearing mice as assessed by immunoblotting analysis using whole cell lysates, whereas the amounts of other TCR chains were relatively unchanged. However, these changes were due to the increase of contaminating Mac-1+ cells in the spleen of tumor-bearing mice because: 1) the removal of Mac-1+ cells led to the restoration of CD3-zeta and p56lck; and 2) CD3-zeta was clearly present when the preparation was solubilized with ionic detergent. Fc receptor gamma chain detected in the preparation from tumor-bearing mice disappeared along with the removal of Mac-1+ cells. These observations were further supported by the finding that addition of Mac-1+ cells from tumor-bearing mice to normal T cells resulted in loss of CD3-zeta, leaving CD3-epsilon largely intact. When T cells from tumor-bearing mice were highly purified by depletion of Mac-1+ cells, these T cells contained normal amounts of CD3-zeta at mRNA, protein, and surface levels, and expressed the properly assembled TCR complex on their cell surface. Moreover, stimulation of the TCR in these T cells by anti-TCR antibodies resulted in a comparable Ca2+ mobilization to that observed in normal T cells. These results suggest that no structural changes occur in TCR complex in our tumor-bearing mice, and that complete depletion of Mac-1+ cells in important to assess the structure of TCR complex.

Animals↗

PubMed2005

Drastic Ca2+ sensitization of myofilament associated with a small structural change in troponin I in inherited restrictive cardiomyopathy.

Six missense mutations in human cardiac troponin I (cTnI) were recently found to cause restrictive cardiomyopathy (RCM). We have bacterially expressed and purified these human cTnI mutants and examined their functional and structural consequences. Inserting the human cTnI into skinned cardiac muscle fibers showed that these mutations had much greater Ca2+-sensitizing effects on force generation than the cTnI mutations in hypertrophic cardiomyopathy (HCM). The mutation K178E in the second actin-tropomyosin (Tm) binding region showed a particularly potent Ca2+-sensitizing effect among the six RCM-causing mutations. Circular dichroism and nuclear magnetic resonance spectroscopy revealed that this mutation does not extensively affect the structure of the whole cTnI molecule, but induces an unexpectedly subtle change in the structure of a region around the mutated residue. The results indicate that the K178E mutation has a localized effect on a structure that is critical to the regulatory function of the second actin-Tm binding region of cTnI. The present study also suggests that both HCM and RCM involving cTnI mutations share a common feature of increased Ca2+ sensitivity of cardiac myofilament, but more severe change in Ca2+ sensitivity is associated with the clinical phenotype of RCM.

Actin Cytoskeleton↗

PubMed2005

Reactive oxygen species (ROS) induce chemical and structural changes on human insulin in vitro, including alterations in its immunoreactivity.

Oxidative stress occurs when the production of reactive oxygen species (ROS) exceeds the endogenous antioxidant defense. Peroxidations induced by ROS are the key of chemical and structural modifications of biomolecules including circulating proteins. To elucidate the effect of ROS on circulating proteins and considering the presence of oxidative stress in Diabetes Mellitus, the effects of ROS, in vitro, on human insulin were studied. We utilized the Fenton reaction for free hydroxyl radical (HO*) generation in presence of human recombinant insulin measuring chemical changes on its molecular structure. The induced changes in insulin were: a) significant increase on absorbance (280 nm) due to phenylalanine hydroxylation (0.023 +/- 0.007 to 0.13 +/- 0.07). b) Peroxidation products formed on amino acids side branches (peroxyl and alcohoxyl group); measured as increased capacity of reduce nitroblue of tetrazolium (NBT) to formazan (0.007 +/- 0.007 to 0.06 +/- 0.02). c) Increased concentration of free carbonyl groups (8.8 +/- 8.7 to 45.6 +/- 20.2 pmoles dinitrophenylhidrazones/nmol insulin) with lost of secondary structure, and d) Modification of epithopes decreasing the insulin antigen-antibody reactivity measured as a decrease in insulin concentration by RIA. In conclusion, the radical hydroxyl in vitro is able to induce molecular modifications on insulin.

Carbon↗

PubMed2006

Structural changes of the Cry1Ac oligomeric pre-pore from bacillus thuringiensis induced by N-acetylgalactosamine facilitates toxin membrane insertion.

The primary action of Cry toxins produced by Bacillus thuringiensis is to lyse midgut epithelial cells in their target insect by forming lytic pores. The toxin-receptor interaction is a complex process, involving multiple interactions with different receptor and carbohydrate molecules. It has been proposed that Cry1A toxins sequentially interact with a cadherin receptor, leading to the formation of a pre-pore oligomer structure, and that the oligomeric structure binds to glycosylphosphatidyl-inositol-anchored aminopeptidase-N (APN) receptor. The Cry1Ac toxin specifically recognizes the N-acetylgalactosamine (GalNAc) carbohydrate present in the APN receptor from Manduca sexta larvae. In this work, we show that the Cry1Ac pre-pore oligomer has a higher binding affinity with APN than the monomeric toxin. The effects of GalNAc binding on the toxin structure were studied in the monomeric Cry1Ac, in the soluble pre-pore oligomeric structure, and in its membrane inserted state by recording the fluorescence status of the tryptophan (W) residues. Our results indicate that the W residues of Cry1Ac have a different exposure to the solvent when compared with that of the closely related Cry1Ab toxin. GalNAc binding specifically affects the exposure of W545 in the pre-pore oligomer in contrast to the monomer where GalNAc binding did not affect the fluorescence of the toxin. These results indicate a subtle conformational change in the GalNAc binding pocket in the pre-pore oligomer that could explain the increased binding affinity of the Cry1Ac pre-pore to APN. Although our analysis did not reveal major structural changes in the pore-forming domain I upon GalNAc binding, it showed that sugar interaction enhanced membrane insertion of soluble pre-pore oligomeric structure. Therefore, the data presented here permits to propose a model in which the interaction of Cry1Ac pre-pore oligomer with APN receptor facilitates membrane insertion and pore formation.

Acetylglucosamine↗

PubMed1995

Effect of long-term treatment with EGb 761 on age-dependent structural changes in the hippocampi of three inbred mouse strains.

Female mice of the inbred strains C57BL/6J, BALB/cJ and DBA/2J were used to determine the possible existence of a genetically-based differential susceptibility to the effects of treatment with an extract of Ginkgo biloba (EGb 761). Timm's silver-sulphide staining method was used to visualize and determine changes in the areas of the hippocampal structures of aged subjects, and more specifically on the projection fields of the mossy fibers which appear to decrease as a function of ageing. Experiments were begun when the animals were 15 months old. Treated animals received EGb 761 (50 mg/kg/day, p.o.) for 7 months in their drinking water. Inter-strain differences existed for the areas of the whole regio inferior, stratum pyramidale, stratum lacunosum moleculare and hilus (CA4) and for the projection field of intra- and infrapyramidal mossy fibers (iipMF) in the CA3 region of the hippocampus. Chronic treatment with EGb 761 significantly increased the projection field of iipMF and significantly reduced the area of the stratum radiatum, as compared with control mice. No differential sensitivity to EGb 761 existed among the mouse strains tested. Antioxydint properties of EGb 761 may explain its neuroprotective and neurotrophic actions on the hippocampus, and might explain certain improvements in memory and other cognitive functions in both humans and experimental animals.

Aging↗

PubMed1983

Transient structural change in hepatic DNA of rats chronically exposed to dimethylnitrosamine.

Structural analysis by chromatography on benzoylated-DEAE-cellulose (BD-cellulose) has been made of hepatic DNA from rats treated for up to 21 weeks with dimethylnitrosamine (DMN). The carcinogen (1 mg/kg body wt) was administered on a daily basis by intraperitoneal injection. By comparison with preparations from saline-treated controls, the proportion of DNA retained by benzoylated-DEAE-cellulose in the presence of 1.0 M NaCl was increased by administration of the carcinogen. Variation in the result, dependent upon the time after the final dose, suggested a complex relationship between structural damage to DNA and duration of treatment. Structural damage was confirmed by S1 nuclease digestion. The observations imply that in the course of chronic administration, increasing time is required to complete DNA repair processes operative in rat liver.

Animals↗

PubMed1997

Structural changes with aging in cortical bone of the human tibia.

Structural modifications are considered to play a significant role in the age-related alterations of bone quality and strength. Senescent compact bone is characterized by an increasing heterogeneity of aspects, including high numbers of lowly mineralized osteons as well as the presence of osteons with hypermineralized lamellae or with a notched haversian canal wall, and of double-zone osteons. These latter three types of osteons are different from the structures involved in the haversian remodeling. In the present study, blocks of midshaft tibia from 7 young men (18-39 years), 14 aged men (50-92 years) and 15 aged women (57-96 years) were embedded in methyl methacrylate in order to perform microradiographic and histomorphometric analysis of undecalcified sections. The intracortical porosity was higher in the aged men than in the young ones, as were the numbers of haversian structures and, to a lesser extent, the diameters of the haversian canals. The aged women showed the same tendency, with cortical porosity still higher than in the men. The osteons with hypermineralized lamellae, those with a notched canal and the double-zone osteons appear to constitute large subgroups of the total haversian population, even in the early adult life. Among them, only the osteons with a notched canal wall increased in frequency with age. The 3 types are much more numerous than the structures involved in the typical haversian remodeling. The correlations between their frequencies as well as their significant topographic association corroborates the hypothesis that the hypermineralized lamellae may crumble down because of their excessive brittleness, giving rise to the haversian canals with notched walls. These enlarged canals could be refilled by bone apposition and result in the double-zone osteons. The 3 types of osteons could constitute different steps of one mechanism of bone desintegration and repair occurring very progressively, which might contribute to modify the bone quality and to increase the intracortical porosity.

Adolescent↗

PubMedDate not supplied

[Structural changes in chromatin of heat shock protein 70 gene of Drosophila during transcription].

Using "protein-image" hybridization technique combined with various crosslinking methods, for formaldehyde-prefixed nuclei we have analysed changes induced by activation in the chromatin structure of HSP-70 genes. From the crosslinking data it follows that chromatin of actively transcribed genes undergoes some structural rearrangements resulting in certain weakening of the contacts between DNA and the globular parts of histones so that the histones remain bound to DNA through their N-terminal regions. In addition, there have been found two specific regions with a reduced content of histones: the 5'-promoter of HSP-70 gene and a region distanced by approximately 1 k.b. from the 3'-end of the HSP-70 gene.

Animals↗

PubMed1988

[Structural changes in the neuropil of the frontal cortex in schizophrenia].

Samples of the prefrontal cortex neuropile autopsied from schizophrenic patients were subjected to electron microscopy. Dystrophic changes were found in the dendrites: pronounced swelling with microtubuli reduced in number or totally absent and mitochondria swollen. Synaptic changes were generally of a functional nature but presynaptic endings were found degenerating with a dense type. Myelinated fibers of various diameters showed pathologic changes. These findings are seen as a structural background for integrative and informative processes deterioration in the prefrontal cortex of schizophrenic patients.

Adult↗

PubMed1985

[Structural changes in the gastric mucosa in experimental hyperthyroidism].

Using a structural and functional analysis experiments on rats have shown the morphological substrate of the impaired pepsin secretion in experimental hyperthyroidism. It has been established that enhancement of the proteolytic activity of gastric juice at early times of hyperthyroidism is linked with activation of biosynthetic processes in the chief gastric cells. Under the conditions of prolonged hyperthyroidism, the reduced proteolytic activity of gastric juice is caused by inhibition of both bioenergetic and biosynthetic processes in the chief cells.

Animals↗

PubMed1982

Analysis of RNA polymerase by trypsin cleavage. Different structural changes produced by heparin and DNA.

Alterations in RNA polymerase structure can be detected using initial trypsin cleavage rates as a conformational probe. Both template (poly[d(A-T) . d(A-T)] and the RNA polymerase inhibitor, heparin, alter the rates at which the subunits of the enzyme are cleaved. However, while the presence of poly[d(A-T) . d(A-T)] slows the cleavage of subunits beta, sigma, and alpha by trypsin, heparin accelerates the cleavage of beta and sigma. Furthermore, the presence of heparin does not prevent the effect of poly[d(A-T) . d(A-T)] on the beta and sigma cleavage rates. Thus, heparin does not eliminate the interaction between DNA and RNA polymerase. That heparin does alter the nature of this interaction is demonstrated by the fact that template decreases the trypsin cleavage rate of subunit alpha in the absence, but not in the presence, of heparin. Like heparin, the addition of RNA to the reaction increases the accessibility of beta and sigma to trypsin. Hence the interaction of heparin with RNA polymerase may mimic the product, rather than the template, interaction.

DNA-Directed RNA Polymerases↗

PubMed1975

Functional and structural changes in isolated rabbit liver mitochondria induced by fluorodichloromethane.

Fluorodichloromethane caused changes in substrate respiration rates and also in adenosine diphosphate (ADP)-stimulated rates of oxidation of both succinate and glutamate. Active swelling of mitochondria also occurred, but only in the presence of magnesium ion. ADP/O ratios were not significantly affected by the fluorocarbon. State IV respiration was stimulated, and the respiratory control ratio was linearly reduced with increased levels of fluorocarbon when succinate was used as substrate. Glutamate-stimulated respiration was greatly affected by the presence of the halocarbon but contrasted to the succinate responses. Low levels of fluorocarbon stimulated the state IV rate with glutamate whereas higher concentrations inhibited respiration. States III and IV respiration were completely inhibited by levels of 4.7 mg/ml of fluorodichloromethane when the nicotinamide adenine dinucleatide (NADH)-linked substrate was used. The NADH-linked substrate was more sensitive to the fluorocarbon treatment than the flavoprotein-linked substrate. The respiratory control ratio reached 1.0 at one-half the concentration required to elicit the same response with the flavoprotein-linked substrate, which suggested that NADH-dehydrogenase was inhibited. Active swelling of mitochondria occurred in the presence of magnesium and fluorocarbon, greatly exceeding controls, suggesting a loss of structural integrity and osmoregulation capacity. Increased rates of reduction of exogenously added cytochrome c also suggested changes in membrane integrity at higher fluorocarbon site of action of this compound is probably not the NADH-dehydrogenase system but the membrane system per se. Structural changes in the membrane system could account for the reported respiratory inhibition.

Adenosine Diphosphate↗

PubMed2002

Spectroscopic analysis of low pH and lipid-induced structural changes in type A botulinum neurotoxin relevant to membrane channel formation and translocation.

Botulinum neurotoxin (BoNT) is an extremely toxic protein to animals and humans. In its mode of action, one of its subunits mediates its translocation by integrating itself into the membrane bilayer. We have examined the membrane channel activity of type A BoNT (BoNT/A) and its heavy (H) chain in planar lipid membrane under various pH conditions to understand the possible role of the channel activity in the translocation of the BoNT/A light (L) chain under physiological conditions. Only BoNT/A H chain, and not the BoNT/A, exhibited membrane channel activity for translocation of ions. The H chain-induced increase in conductance did not require a pH gradient across the lipid membrane, although it was enhanced by a pH gradient. To understand the molecular basis of the membrane channel activity and the translocation of the L chain, the secondary structure of BoNT/A and its H and L chains were analyzed using circular dichroism (CD) and Fourier-transform infrared (FT-IR) spectroscopy at different pH values. BoNT/A showed no structural alternation upon acidifying the buffer pH. However, an increase in beta-sheet content of BoNT/A H chain at low pH was noted when examined by FT-IR. The L chain structure significantly changed with decrease in pH, and the change was mostly reversible. In addition, the neurotoxin and its subunit chains induced a partially reversible aggregation of liposomes at low pH, which indicated their integration into the lipid bilayer. Temperature-induced denaturation studies of BoNT/A H chain indicated major structural reorganization upon its interaction with membrane, especially at low pH.

Biological Transport↗

PubMed1997

Changing structure to improve function: one academic health center's experience.

Academic health centers (AHCs) have been under siege for the past few years, with decreased federal and state funding for educational and research programs and increasing competition in the health care marketplace. In addition, many AHCs are burdened with the bureaucratic red tape of large educational institutions, which makes agility in responding to a demanding health care market difficult. The authors describe the response to these threats by Oregon Health Sciences University (OHSU), an approach that has been different from those of most similar institutions. OHSU chose to change its structure from being part of the state system of higher education to being an independent public corporation. The authors outline the political process of building widespread support for the legislation passed in 1995, the key features of the restructuring, the challenges faced before and after the transition to a public corporation, and lessons learned in this metamorphosis to a new form.

Academic Medical Centers↗