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PubMed1994

DNase I footprinting of triple helix formation at polypurine tracts by acridine-linked oligopyrimidines: stringency, structural changes and interaction with minor groove binding ligands.

We have investigated the binding of short (10 base) acridine-linked triplex-forming oligonucleotides to the target sequence A6G6.C6T6 by DNase I footprinting. Specific binding is detected at low pH (< 6.0) for 5'-Acr-T5C5 and 5'-Acr-5BrU5(5Me)C5. The sequence T5C5, lacking the acridine modification, binds less strongly, though specific binding is still evident. 5'-Acr-T5C5 produces footprints at slightly lower concentrations than 5'-Acr-5BrU5(5Me)C5. All three oligonucleotides produce enhanced DNase I digestion at the 3'-end of the target purine strand, suggesting that there is a DNA structural change at the triplex-duplex boundary. Target sequences AnG4A and TAC3Tn, containing one and two triplex mismatches, show no interaction with the acridine-free oligonucleotide, but bind the acridine-linked oligonucleotides. In these secondary binding modes the third strand is positioned so that the mismatches are located at the 3'-end of the oligonucleotide. Mithramycin and distamycin, binding in the minor groove to GC- and AT-rich sequences respectively, abolish triple helix formation.

Acridines↗

PubMed1985

Proton NMR of aequorin. Structural changes concomitant with calcium-independent light emission.

Aequorin, a Ca(II)-sensitive bioluminescent protein from jellyfish, emits light at 469 nm from an excited state of a substituted pyrazine (oxyluciferin) which results from the oxidation of a chromophore molecule that is noncovalently bound to the protein. The chromophore is oxidized when Ca(II) or other activating metal ions are bound by aequorin. In the absence of Ca(II), spontaneous emission of light, referred to as Ca(II)-independent light emission, occurs at a rate less than 10(-6) of that for Ca(II)-induced emission. Proton nuclear magnetic resonance (NMR), circular dichroism (CD), and fluorescence were used to study structural changes of aequorin accompanying Ca(II)-independent light emission. Time course studies by 1H NMR and CD demonstrate that as a result of Ca(II)-independent light emission, aequorin progressively changes from a rigid, fully active form showing little segmental mobility to a practically unfolded, discharged (i.e., inactive) form in which a number of amino acid residues are significantly mobile. This slow discharged protein (SDP) is distinct in nature and conformation from aequorin which has been discharged by Ca(II), i.e., the blue fluorescent protein. The rate of Ca(II)-independent discharge of aequorin is substantially reduced in the presence of excess Mg(II); the time constant for inactivation at 5 degrees C is 30 days with no Mg(II) present and 70 days with Mg(II) present. The NMR spectra are nearly identical at a given stage of inactivation whether or not Mg(II) is present. Oxyluciferin remains bound to SDP. If it is removed, however, by column chromatography, the resulting apo-SDP partially refolds, and the segmental mobility acquired in the formation of SDP is significantly attenuated particularly for some of the aromatic amino acid residues.

Aequorin↗

PubMed1975

Structural changes in myosin during contraction and the state of ATP in the intact frog muscle.

The reactivity of myosin to [14C]-labeled N-ethylmaleimide ([14C]NEM) or to tritium was determined in functionally different frog muscles. The incorporation of [14C]NEM into myosin decreased during isotonic or isometric contractions, as compared to resting muscle. The cysteine residues which were protected during contraction were not involved in the ATPase activity or the actin-binding ability of myosin. Peptide mapping revealed that several residues were protected simultaneously. The incorporation of tritium into the peptide N-H groups of myosin was also decreased during muscle activity. These data support the idea that activation and subsequent contraction of muscle are correlated with structural changes in the myosin molecule. The reactivity of myosin to [14C]NEM was increased when the muscle was stretched to 140% rest length and treated with iodoacetate to deplete ATP. Based on in vitro experiments and on literature data, it is suggested that in the resting muscle myosin contains bound MgATP which decreases the rate of incorporation of [14C]NEM into myosin and that upon the irreversible loss of ATP the rate increases. 31P nuclear magnetic resonance signals from a number of phosphates were detected in the intact frog muscle. The data indicated that the minimum concentration of ATP in the muscle is 3 mM, a value which agrees with that of chemical determination. The characteristic chemical shifts, coupling constants, and line widths of ATP in the muscle were considerably altered from that of either free ATP in aqueous solutions or ATP in perchloric acid extracts of muscle.

Actins↗

PubMed2003

Structural changes of water molecules during the photoactivation processes in bovine rhodopsin.

Internal water molecules of rhodopsins play an important role in stabilizing the crucial ion pair comprised by the protonated retinal Schiff base and its counterion. Previous low-temperature FTIR spectroscopy of archaeal rhodopsins observed water O-D stretching vibrations at 2400-2100 cm(-1) in D(2)O, corresponding to strong hydrogen bonds. Since a water molecule bridges the protonated Schiff base and an aspartate in archaeal rhodopsins, the observed water molecules presumably hydrate the negative charges in the Schiff base region. In contrast, the FTIR spectroscopy data of bovine rhodopsin presented here revealed that there are no spectral changes of water molecules under strongly hydrogen-bonding conditions (in the range <2400 cm(-1) for O-D stretch) during the photoactivation processes. The only observed water bands were located in the >2500 cm(-1) region that corresponds to weak hydrogen bonding. These results imply that the ion pair state in vertebrate visual rhodopsins is stabilized in a manner different from that in archaeal rhodopsins. In addition, the internal water molecules that hydrate the negative charges do not play important role in the photoactivation processes of rhodopsin that involve proton transfer from the Schiff base to Glu113 upon formation of Meta II. Structural changes of the H-D exchangeable peptide amide of a beta-sheet are observed upon formation of metarhodopsin II, suggesting that motion of a beta-sheet is coupled to the proton transfer reaction from the Schiff base to its counterion.

Animals↗

PubMed1983

High-pressure nuclear magnetic resonance studies of hemoproteins. Pressure-induced structural changes in the heme environments of ferric low-spin metmyoglobin complexes.

In order to gain an insight into nonbonded interactions in the heme microenvironments of hemoproteins, proton NMR spectra of the cyanide and methylamine complexes of metmyoglobin and its derivatives reconstituted with deutero- and meso-hemins in H2O were studied under high pressures. The exchangeable NH proton of distal histidyl imidazole exhibits substantial pressure-induced shift while the proximal histidyl NH proton shows no pressure effect for the cyanide complexes. The heme peripheral proton signals, especially 5- and 8-methyl and vinyl C alpha H resonances, were also affected by pressure. These observations are interpreted as arising from pressure-induced structural changes in the heme crevice in which the pressure effects are localized to the distal side rather than the proximal side and from possible changes in the van der Waals contacts at the heme periphery with nearby amino acid residues.

Animals↗

PubMed2001

Structural changes in the auricles of the rat heart after local ionizing irradiation.

BACKGROUND AND PURPOSE: Irradiation of the heart may lead to late cardiovascular complications and depending on the dose to cardiac-related death. There is increasing evidence that left atrial appendages play an important role in left ventricular filling especially in cardiac disease. The aim of the present study was to investigate the radiation response of the atria of the rat heart (auricles in particular) at morphological, histological and transcriptional level. MATERIAL AND METHODS: Sprague-Dawley rats were irradiated with a single dose locally on the heart (0-22.5 Gy). End-diastolic diameters of left auricles were measured during evaluation of cardiac function. Histopathological evaluations were performed at various time points up to 16 months post irradiation. Changes in mRNA expression of procollagen types I and III and pro-fibrogenic cytokines (TGF-beta1 and IL-1beta) were investigated using competitive PCR. RESULTS: Irradiation leads to a dose-dependent decrease in end-diastolic diameter of the left auricles. This decrease was observed at 4 months post-irradiation, where no gross damage of the ventricle has been reported. Histologically, epicardial fibrosis was found already 1 month post irradiation, and the frequency/severity of the structural changes appeared to be dose-dependent and progressive with time post irradiation. At 9 months, fibrosis was observed in all three layers (epicardium, myocardium and endocardium) of both auricles. On the level of gene expression, increases in procollagen types I and III were observed at 12 and 3 months post irradiation, respectively. Increases in IL-1beta and TGF-beta1, cytokines known to influence collagen deposition at different levels, preceded the upregulation of procollagen mRNA. CONCLUSIONS: Auricles of the rat heart show a marked pathological response to ionizing radiation, characterized by generalized accumulation of collagen (fibrosis) and a reduction of end-diastolic diameter. The reduction of auricular volume and loss of elasticity will negatively contribute to the pump function of the irradiated ventricle.

Animals↗

PubMed1985

Structural changes in mouse small intestinal villi following lower body hyperthermia.

Heating an exteriorised loop of mouse small intestine resulted in marked changes in the shape of the villi as reported earlier. However, the exteriorisation techniques resulted in non-uniformity in both temperature and effect around circumference of intestine and, in addition, the extent to which handling contributed to the observed damage was not known. The work has therefore been extended using lower-body heating in the temperature range 37.5 degrees - 43.0 degrees C. Heating in the temperature range 37.5 degrees C to 41.0 degrees C produced minimal to moderate structural changes, manifested as scattered, vertically collapsed villi amongst predominantly "normal" villi. No villi showed conical or rudimentary forms of collapse. Such villi were, however, seen after heating at 41.5 degrees C and were greatly increased in number after heating at 42.0 degrees C. The most severe damage was observed after heating at 43.0 degrees C. Although the lower body heating method gave information which was less complicated by technical considerations, the hyperthermic damage observed was qualitatively similar to that previously seen following local administration of hyperthermia to an exteriorised loop of intestine. Direct quantitative comparisons between the two methods of heating are difficult because of differences in equilibration time and temperature. However, using a comparable heating time, less damage was scored following the exteriorisation technique compared with in situ heating.

Animals↗

PubMed1993

An absence of structural changes in the proximal femur with osteoporosis.

The hypothesis that osteoporosis occurs not as a preferential loss of the tensile trabeculae but as a general loss of bone was tested by using bone mineral densitometry and an indentation test on dissected proximal femora. As osteoporosis advanced a significantly correlated decrease was found in both bone mineral density and mechanical properties between the principal compressive and tensile trabeculae. The decrease correlated with a decrease in the Singh index. These findings led to the conclusion that a sequential bone loss from the tensile trabeculae to the compressive ones did not occur as Singh reported, but instead a generalized loss of bone mineral in both the tensile and compressive trabeculae supervened. The structural changes, on which the grading system by Singh was based, were not observed in the proximal femur affected by osteoporosis.

Aged↗

PubMed1984

The use of double mutants to detect structural changes in the active site of the tyrosyl-tRNA synthetase (Bacillus stearothermophilus).

In a previous study, a mutant of tyrosyl-tRNA synthetase in which a threonine residue (Thr51) was converted to proline dramatically improved the affinity of the enzyme for its ATP substrate. How does Pro51 improve the enzyme's affinity for ATP? A priori, Pro51 might interact directly with the ATP, or it might distort the polypeptide backbone and thereby force new or improved contacts elsewhere from the enzyme to ATP. By making mutants of the Pro51 enzyme at two residues that make hydrogen bonds to the ATP substrate, we show that Pro51 greatly improves the strength of one of these contacts. Thus the propagation of a structural change in an enzyme induced by mutation may be detected by the introduction of further mutations.

Amino Acyl-tRNA Synthetases↗

PubMed2002

The effects of estrogen-responsive element- and ligand-induced structural changes on the recruitment of cofactors and transcriptional responses by ER alpha and ER beta.

Estrogen signaling is mediated by ER alpha and -beta. ERs are converted from an inactive form to a transcriptionally active state through conformational changes induced by ligand and estrogen-responsive element (ERE) sequences. We show here that ER alpha and ER beta bind to an ERE independently from ER ligands. We found that although the binding affinity of ER beta for an ERE is 2-fold lower than that of ER alpha, both ERs use the same nucleotides for DNA contacts. We show that both EREs and ligands are independent modulators of ER conformation. Specifically, the ERE primarily determines the receptor-DNA affinity, whereas the structure of the ER ligand dictates the affinity of ER for particular cofactors. We found that the ligand-dependent cofactor transcriptional intermediary factor-2, through a distinct surface, also interacts with ER alpha preferentially and independently of ligand. The extent of interaction, however, is dependent upon the ER-ERE affinity. In transfected cells, ER alpha is more transcriptionally active than ER beta. The ERE sequence, however, determines the potency of gene induction when either ER subtype binds to an agonist. Antagonists prevent ERs from inducing transcription independently from ERE sequences. Thus, ERE- and ligand-induced structural changes are independent determinants for the recruitment of cofactors and transcriptional responses. The ability of ER alpha to differentially recruit a cofactor could contribute to ER subtype-specific gene responses.

Animals↗

PubMed1996

Spin-spin interactions between the Ni site and the [4Fe-4S] centers as a probe of light-induced structural changes in active Desulfovibrio gigas hydrogenase.

In typical NiFe hydrogenases like that from Desulfovibrio gigas, the active state of the enzyme which is obtained by incubation under hydrogen gas gives a characteristic Ni-C electron paramagnetic resonance (EPR) signal at g = 2.19, 2.14, and 2.01. The Ni-C species is light-sensitive, being converted upon illumination at temperatures below 100 K in a mixture of different Ni-L species, the most important giving an EPR signal at g = 2.30, 2.12, and 2.05. This photoprocess is considered to correspond to the dissociation of a hydrogen species initially coordinated to the Ni ion in the Ni-C state. When the [4Fe-4S] centers of the enzyme are reduced, the proximal [4Fe-4S]1+ cluster interacts magnetically with the Ni center, which leads to complex split Ni-C or split Ni-L EPR spectra only detectable below 10 K. In order to probe the structural changes induced in the Ni center environment by the photoprocess, these spin-spin interactions were analyzed in D. gigas hydrogenase by simulating the split Ni-L spectra recorded at different microwave frequencies. We shown that, upon illumination, the relative arrangement of the Ni and [4Fe-4S] centers is not modified but that the exchange interaction between them is completely canceled. Moreover, the rotations undergone by the Ni center magnetic axes in the photoconversion were determined. Taken together, our results support a Ni-C structure in which the hydrogen species is not in the first coordination sphere of the Ni ion but is more likely bound to a sulfur atom of a terminal cysteine ligand of the Ni center.

Binding Sites↗

PubMed1990

A protein structural change in aglycosylated IgG3 correlates with loss of huFc gamma R1 and huFc gamma R111 binding and/or activation.

Glycosylated chimeric mouse-human anti-NIP IgG3 antibody produced by growth of the J558L mouse B cell plasmacytoma is characterised with respect to the single carbohydrate chain at Asn-297 in the CH2 domain indicating that the mouse cell glycosyl transferases dictate the pattern of glycosylation rather than the human CH region of the heavy chain. Additionally, three unusual alpha-galactose-containing oligosaccharides are reported. Only the Fc region has detectable carbohydrate. Aglycosylated anti-NIP IgG3 antibody has been produced by cell growth in the presence of the antibiotic tunicamycin. Functionally, whilst the glycosylated intact IgG3 interacts with human Fc gamma R111 expressed on human killer (K) cells to trigger antibody-dependent cellular cytotoxicity the aglycosylated intact IgG3 fails to trigger cell lysis, localising the site on IgG for triggering human Fc gamma R111 mediated functions to the CH2 domain. The monomeric aglycosylated trypsin Fc fragment inhibits human Fc gamma R1 recognition by U937 cells 115-fold less well (K50 = 2 microM) than does glycosylated Fc (K50 = 17 nM), confirming that aglycosylation disrupts the site for human Fc gamma R1 within the CH2 domain and indicating that the trypsin Fc fragments reflect the functional properties of the intact IgG glycoforms. Structurally, 1H NMR shows that the absence of carbohydrate at Asn-297 results in a small and localised protein structural change in the vicinity of the reporter group His-268 within the CH2 domain. The site on IgG for triggering human Fc gamma R111 mediated functions is then localised to the vicinity of His-268. The profound impact of aglycosylation on human Fc gamma R1 recognition implies structural disruption of the proposed site for human Fc gamma R1 in the lower hinge region of IgG (residues 234-239), proximal to His-268.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1981

L-Arabinose-binding protein-sugar complex at 2.4 A resolution. Stereochemistry and evidence for a structural change.

The L-arabinose molecule (in the C1 pyranose chair conformation) has been fitted to the electron density corresponding to the bound sugar in the 2.4 A resolution Fourier map of the L-arabinose-binding protein. The sugar molecule is buried in the cleft between the two lobes of the bilobate protein. All sugar hydroxyls are hydrogen-bonded to side chain residues: beta-OH(1) to Lys-10 and Asp-90, OH(2) to Lys-10, OH(3) to Asn-205 and Glu-14 (possibly via a water molecule), and OH(4) to Asn-232. Lys-10, Glu-14, and Asp-90 are associated with one domain while Asn-205 and Asn-232 are lodged in the other. Protein structural change accompanying binding is indicated by the inaccessibility of the bound L-arabinose to the aqueous environment.

Arabinose↗

PubMedDate not supplied

[Structural changes in actin filaments during binding with phosphofructokinase (F-protein), detected using an optical diffraction method].

It has been previously shown by us that phosphofructokinase (F-protein) binds to rabbit skeletal muscle F-actin and reconstituted thin filaments forming ordered bundles. Upon low molar ratios of phosphofructokinase to actin in the complex bundles the enzyme molecules are arranged between actin filaments regularly in the form of crossbridges. The increase of phosphofructokinase: actin ratio up to equimolar one and more leads to the filling of the space between actin filaments with phosphofructokinase-molecules. In these bundles the inclined cross striation with axial repeat of about 7.0 nm is clearly seen. Optical diffraction analysis of the micrographs revealed new features in the structure of such complexes in comparison with F-actin and reconstituted thin filaments. Optical diffraction patterns from F-actin and reconstituted thin filaments exhibit the first (35.5 nm) and sixth (5.9 nm) layer lines typical of F-actin helix structure. On the optical diffraction patterns from the complex bundles the meridional reflection of about 7.2nm is present, that is not observed on the optical diffraction patterns from F-actin alone. This reflection is characteristic of optical diffraction- and X-ray patterns of myosin filaments and is the sixth order of axial period of their structure (42.9 nm/6). The structural changes occurring upon binding is supposed to be important for the mutual regulation of functional activity of enzymes and actin-containing filaments in muscle.

Actins↗

PubMed1997

Structural changes in the renal proximal tubular cells induced by iodinated contrast media.

The renal morphologic changes induced by intravenously injected contrast media (CMs) were studied in 40 Wistar rats which had been deprived of water 24 h before the CM injection. In the first part of the investigation, the kidneys were fixed by perfusion for light and electron microscopy 2 h after injection of 3 g iodine/kg of iopamidol, iobitridol or iohexol. Control animals received physiologic saline. In the second part of the study, the fixation was performed 48 h after the injection of the corresponding dose of iobitridol or iohexol. The structural changes were semiquantitatively evaluated by two independent observers unaware of the agent injected. The lysosomes of the proximal convoluted tubular cells showed moderate changes 2 h after the iopamidol injection. Iobitridol and iohexol induced prominent lysosomal alterations with signs of cytoplasmic injury. After 48 h, the changes induced by iobitridol had almost disappeared, whereas the iohexol group still showed a statistically significant vacuolization. Although the general physicochemical properties of iobitridol and iohexol appear similar in vitro, the different lysosomal alteration might reflect differences in their characteristics in vivo.

Animals↗

PubMed1999

Rapid structural changes in nerve fibers and cells associated with their excitation processes.

In a variety of nerve fibers, cells and other excitable tissues, the electric responses to electric stimuli were found to be accompanied by a transient swelling of the tissues. The rising phase of this swelling coincides with that of the electric response. By use of a heat-sensor made of polyvinylidene fluoride film, it was also shown that the electric responses of many types of excitable tissues are accompanied by simultaneous heat production. To elucidate the origin of this swelling and heat production, the process of Ca2+-Na+ exchange in synthetic anionic gel beads and rods was investigated. It is asserted that the observed signs of nerve excitation are manifestations of a rapid structural change of the cortical gel layer of the protoplasm, plasmalemma-ectoplasm complex. The importance of the rapid movement and rearrangement of water molecules in the cortical gel layer in association with excitation processes is emphasized.

Animals↗

PubMed1986

Genetic recombination between multiple markers of bacteriophage T4. III. A mutation which blocks a structural change of DNA required for strand exchange.

T4 phage mutation MCO5 is a non-lethal recessive mutation which blocks recombination between multiple closely linked markers and links to genes 24 and 25. The three-factor cross, which required double exchange flanking the central marker for the formation of wild type recombinant, was blocked by MCO5 mutation. The blockage was restored by the UV irradiation of the parental phage carrying single mutation but not by the UV irradiation of the parental phage carrying double mutation. The MCO5 mutant reduced the rescue of the markers of UV-irradiated phage, although it had normal levels of sensitivity to UV in both single and multiple infections. From these results, it is concluded that MCO5 mutation blocks a structural change of DNA which is necessary for receiving DNA segment.

Bacteriophages↗

PubMed2000

pH-dependent reversible inhibition of violaxanthin de-epoxidase by pepstatin related to protonation-induced structural change of the enzyme.

The redox enzyme violaxanthin de-epoxidase (VDE) was found to be sensitive to pepstatin, a specific inhibitor of aspartic protease. The inhibition was similar to that of aspartic protease in that it was reversible and accompanied by the protonation of the enzyme. Of the two peaks of VDE appearing on anion exchange chromatography, VDE-I predominated at pH 7.2. On lowering the pH of the chromatography, VDE-I decreased and VDE-II increased. Furthermore, re-chromatography of either peak yielded both peaks. These results suggest that VDE-I and VDE-II are interconvertible depending on pH, and thus, they represent the de-protonated and protonated forms of the enzyme, respectively. Presumably the protonation-induced structural change of the enzyme is responsible for the interaction with pepstatin, and also with substrate.

Chromatography, Ion Exchange↗