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PubMed2001

The 2.7 A crystal structure of the activated FERM domain of moesin: an analysis of structural changes on activation.

Moesin binds to a large range of proteins through its N terminal FERM (band 4.1, ezrin, radixin, moesin) domain. In full-length moesin isolated from cells, this binding is masked by binding to the C-terminal domain of moesin (C-ERMAD). Activation takes place by phosphorylation of Thr 558 in the C-ERMAD, which releases the C-ERMAD. A recently determined crystal structure of a noncovalent complex of the FERM and C-ERMAD domains showed for the first time that the structure of the FERM domain consists of three subdomains, each of which is similar to known structures. The structure reported here also contains a unique 47-residue helix pointing away from the FERM domain at the start of the alpha domain, in agreement with secondary structure predictions. Removal of the C-ERMAD does not result in a huge rearrangement of the FERM domain, but comparison with the activated radixin structure shows a consistent set of small changes. Not surprisingly, the exposed C-ERMAD binding area interacts in crystal contacts. More interestingly, a negatively charged peptide binds to the inositol site in a crystal contact and causes a greater conformational change in the structure than inositol.

Amino Acid Sequence↗

PubMed1990

Structural changes in astrocytes induced by seizures in a mode of temporal lobe epilepsy.

Injection of iron-chloride solution unilaterally into the hippocampus of albino rats induced transient seizure activity which lasted approximately 2 weeks. Frontal and parietal cortices of experimental rats, control rats which received NaCl injections, and unoperated normal rats were compared by means of a Golgi stain which demonstrated astrocytes and their processes in their entirety. Morphometric analysis showed that cortical astrocytes of rats having intermittent seizure activity over a prolonged period were significantly larger than cortical astrocytes of control rats. These findings indicate that seizure activity causes structural brain changes at anatomical sites distant from the hippocampal seizure focus. Similar phenomena may contribute to the development of psychiatric and neurological changes in the epileptic patient.

Animals↗

PubMedDate not supplied

[Possible role of structural changes in ATP hydrolysis by subfragment-1 and myosin].

Dependence of the rate of ATP hydrolysis with subfragment-I and temperature of SF-I, denaturation on the concentration of heavy water in solution was studied. The value of kinetic isotope effect V/Vx linearly increases with the rise of the volume portion of heavy water in solution and at X-1 it equals 1.9. The temperature of protein denaturacticn increases with X rise, the pattern of this relationship looking as an arched curve. The results differ from those earlier obtained on myosin which points to the absence of essential contribution of structural dynamic changes to enzymic hydrolysis of ATP by subfragment-I.

Adenosine Triphosphate↗

PubMed1987

Reversibility of structural changes in the resistance vessels in hypertension: a review of studies with pindolol.

1. In recent years evidence has accumulated which indicates that although various beta-adrenoceptor antagonists are equally effective in lowering blood pressure in patients with essential hypertension the mechanisms of action of the different drugs are heterogeneous. 2. Pindolol, a beta-adrenoceptor antagonist with pronounced intrinsic sympathomimetic activity (ISA) appears, to some extent, to act via peripheral vascular mechanisms. 3. Following prolonged treatment with pindolol in essential hypertension peripheral vascular resistance at maximal vasodilatation has been found to be decreased compared with the pretreatment values suggesting that the structural vascular changes characteristic of established hypertension may be reversible.

Humans↗

PubMedDate not supplied

Regression of cardiovascular structural changes by antihypertensive treatment. Functional consequences and time course of reversal as judged from clinical studies.

Echocardiographic studies have shown a decrease in left ventricular (LV) wall thickness and an improvement in LV function during antihypertensive treatment. A reduction in LV mass parallels the reduction in LV wall thickness during the first year of antihypertensive treatment, but thereafter favorable changes in LV wall thickness, cardiac output, and total peripheral resistance may be recorded in spite of a constant LV mass. The reason for this is that LV mass is defined by LV wall thickness and LV end-diastolic diameter, and that LV mass may stay unchanged if LV wall thickness decreases when LV diameter increases. This pattern of change is to be expected since LV distensibility and, hence, LV end-diastolic diameter may increase when LV wall thickness decreases. The effect of treatment may thus be divided into two main phases--an initial phase with a reduction in LV mass and a reduction in cardiac output and no change in total peripheral resistance--and a second phase with a constant LV mass but an increase in cardiac output to the pretreatment level again and a concomitant decrease in total peripheral resistance. The increase in stroke volume and cardiac output during this second phase of treatment is mainly dependent on an increase in end-diastolic volume, most likely explained by improved LV compliance when LV wall thickness decreases. The concomitant decrease in total peripheral resistance is mainly explained by reversal of structural vascular changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗

PubMed2005

Capsule structure changes associated with Cryptococcus neoformans crossing of the blood-brain barrier.

Cryptococcus neoformans is a yeast responsible for disseminated meningoencephalitis in patients with cellular immune defects. The major virulence factor is the polysaccharide capsule. We took advantage of a relevant murine model of disseminated meningoencephalitis to study the early events associated with blood-brain barrier (BBB) crossing. Mice were sacrificed at 1, 6, 24, and 48 hours post-intravenous inoculation, and classical histology, electron microscopy, and double immunofluorescence were used to study tissues and yeasts. Crossing of the BBB occurred early after inoculation, did not involve the choroid plexus but instead occurred at the level of the cortical capillaries, and caused early and severe damage to the structure of the microvessels. Seeding of the leptomeninges was not the primary event but occurred secondary to leakage of cortical pseudocysts. Organ invasion was associated with changes in cryptococcal capsule structure and cell size, which differed in terms of magnitude and kinetics, depending on both the organs involved, and potentially, on the bed structure of the local capillary. The rapid changes in capsule structure could contribute to inability of the host immune response to control cryptococcal infection in extrapulmonary spaces.

Animals↗

PubMed1990

[The functional and structural changes in the hematoparenchymatous barrier of the skeletal muscle during starvation].

The data obtained suggest that an increasing oxygen permeability of hematoparenchymatous barrier is a result of structural and chemical changes of biomembranes in rabbits after 7 days of starvation. A significant increase in desaturation of lipids and phospholipids, a decrease of cholesterol level in cytoplasmic and basal membranes were shown along with modifications of vascular endothelium of a metabolic type.

Animals↗

PubMed2004

Tryptophan fluorescence monitors structural changes accompanying signalling state formation in the photocycle of photoactive yellow protein.

Photoactive yellow protein, a small, water-soluble blue-light absorbing photoreceptor protein from Ectothiorhodospira(Halorhodospira)[space]halophila has a structure with two hydrophobic cores, of which the main one houses its light-sensitive chromophore (p-coumaric acid), separated by a central [small beta]-sheet. This photoreceptor protein contains a single tryptophan residue (W119) that is situated at the interface between the central beta-sheet and its N-terminal cap. The fluorescence properties of W119 in the dark state pG (lambda(max)= 328 nm; Phi(fl)= 0.01; nearly pH-independent) are typical for a buried tryptophan in a hydrophobic environment with significant quenching by nearby amino acid residues. Signalling state formation leads to pH-dependent fluorescence changes: At pH values <6.5 the fluorescence emission increases, with a minor blue shift of the emission maximum. Above this pH, the emission maximum of the tryptophan shifts considerably to the red, whereas its total intensity decreases. These results further support the contention that signalling state formation in PYP leads to significant changes in the structure of this protein, even at sites that are at a considerable distance from the chromophore. The nature of these changes in pB, however, depend upon the pH imposed upon the protein: At slightly alkaline pH, which presumably is closest to the pH to which this protein is exposed in vivo, these changes lead to an exposure of the part of the central beta-sheet harbouring W119. At slightly acidic pH the polarity of the environment of W119 is hardly affected by the formation of the signalling state but the quenching of its fluorescence emission, possibly by nearby amino acids, is reduced. On the other hand, its accessibility for quenching by small molecules in the solution is enhanced at acidic and alkaline pH in the signalling state (pB) compared to the dark state (pG). This latter observation points towards a more flexible structure of the N-terminal cap, having a looser interaction with the central beta-sheet in pB.

Acrylamide↗

PubMed1999

Vertebral osteoblastoma: are radiologic structural changes necessary for diagnosis?

BACKGROUND: A case of osteoblastoma localized at the pedicle of the 10th thoracic vertebra is presented. CASE DESCRIPTION: The patient complained of nocturnal back pain not relieved by salycilates, a typical symptom of osteoblastoma. Bone scintigraphy showed a lower thoracic focus of increased osteoblastic activity; however, X-rays, computed tomography, and magnetic resonance images (MRI) were within normal limits, showing only obscure changes that were also noted in the rest of the spine. Repeat MRI with contrast revealed a focal enhancement. After pediculectomy, histopathologic examination confirmed the diagnosis of osteoblastoma. Fifteen months postoperatively, the patient is symptom-free. CONCLUSION: Our case demonstrates that some cases of osteoblastoma may not have the classical radiological appearance. Although non-contrast computed tomography and T1-weighted MRI are mildly positive in some instances, osteoblastoma is best visualized on MRI with gadolinium. Like any other neoplasm, osteoblastoma should be detected and removed early, before it can cause structural bony changes.

Adult↗

PubMed1988

Interparticle interactions and structural changes of nucleosome core particles in low-salt solution.

The structural behavior of the nucleosome core particles in the range of solvent Na+ concentration from 10.45 to 0.45 mM has been studied by small-angle neutron and synchroton radiation X-ray scattering, sedimentation, atomic absorption spectroscopy, density measurements, and circular dichroism. With decreasing salt concentration, the appearance of a scattering peak that is assignable to interparticle interactions, an intraparticle structural transition, a decrease in the sedimentation velocity of the particle, and a release of bound Na+ ions from the particle are all observed concurrently when the ratio of solvent Na+ ions per particle is below approximately 1000. These observations are interpreted to indicate that a release of bound Na+ ions from the particle brings about structural rearrangements and weakens the electrostatic shielding of the particle, and this introduces long-range repulsive ordering of the particle in low-salt solution. Analyses of the scattering data indicate that the rearrangement within the core particle in low-salt solution is slight, changing the particle's shape slightly from cylindrical to a more spherical form by moving the center of the mass of the DNA somewhat inward with accompanying small decreases in the radii of gyration of both the DNA and the histones.

Animals↗

PubMed1997

Functional and structural changes in the thick ascending limb of Henle's loop in rats with liver cirrhosis.

Five weeks after common bile duct ligation (CBL), Wistar rats had histologically verified liver cirrhosis with sodium retention but without ascites. Plasma concentrations of vasopressin and aldosterone were normal. Glomerular filtration rate was unchanged, although renal plasma flow was increased. A test dose of furosemide (7.5 mg/kg body wt iv) produced significantly greater diuretic (+59%) and natriuretic (+66%) responses in Wistar CBL rats than in sham-operated controls. Stereological examination of kidneys demonstrated a 47% increase in the volume of the inner stripe of the outer medulla, with a 55% increase in the volume of thick ascending limb of Henle's loop (TALH) epithelium in cirrhotic Wistar rats relative to controls. CBL produced a similar degree of liver cirrhosis in vasopressin-deficient Brattleboro rats. However, both functional and structural renal changes observed in cirrhotic Wistar rats were absent in vasopressin-deficient cirrhotic Brattleboro rats. These results suggest a permissive action of vasopressin for the adaptive changes in TALH in rats with experimental liver cirrhosis. Our results are consistent with the hypothesis that increased sodium chloride reabsorption in the TALH may contribute to the early sodium retention that precedes ascites formation in rats with secondary biliary liver cirrhosis.

Animals↗

PubMed2006

Structural changes of the corpus callosum in mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Although previous studies demonstrate significant atrophy of the corpus callosum (CC) in patients with Alzheimer's disease (AD), CC alterations in mild cognitive impairment have not been investigated yet. METHODS: 21 subjects with mild cognitive impairment, 10 with AD and 21 healthy controls were investigated using magnetic resonance imaging. In the mid-sagittal slice the CC was traced manually. Additionally, voxel-based morphometry (VBM) was performed. RESULTS: The CC was significantly smaller in patients with AD compared to healthy controls in both manual tracing and VBM. The atrophy was prominent in rostral parts of the CC. In subjects with mild cognitive impairment, the two rostral CC segments were smaller compared to controls when manually traced. In contrast, VBM revealed no significant difference between subjects with mild cognitive impairment and controls. CONCLUSION: Manual tracing was more sensitive in detecting discrete structural CC changes than VBM. Alterations of the CC in mild cognitive impairment rank in between normal aging and AD, supporting the hypothesis that mild cognitive impairment most often represents a preclinical stage of AD.

Aged↗

PubMed1989

Structural changes in positively and negatively supercoiled DNA.

The effect of superhelical constraint on the structure of covalently closed circular DNA (cccDNA; pBR322) with positive and negative writhe (superturn) has been investigated as a function of decreasing and increasing specific linking difference (mean superhelical density sigma). At low and moderate negative superhelical densities sigma, the overall average structure is maintained in an unwound B-form slightly modified. The overwound cccDNAs with positive writhe differ from those with negative writhe by an absence of cruciform structure. At high negative densities of supercoiling different changes involving the reversal of twist handedness are shown to lead to the formation of DNA segments in a conformation identical to the left-handed component of form V DNA.

Circular Dichroism↗

PubMed1987

Persistent structural change in replicating hepatic DNA isolated from diethylnitrosamine-treated rats.

Structural analysis, by benzoylated O-(diethylaminoethyl) (DEAE)-cellulose chromatography, was made of DNA from the livers of rats receiving 100 mg/kg diethylnitrosamine and subsequently subjected to partial hepatectomy. Under these conditions, different DNA labelling procedures permit damage to be associated with pre-existing or newly synthesised DNA. Persistent single stranded regions could be detected in DNA isolated more than 3 days after carcinogen treatment only if the animals were subjected to hepatectomy. This damage was attributable to lesions impeding DNA replication. Induction of proliferative activity up to at least 14 days after nitrosamine treatment made manifest DNA damage, the extent of which was not decreased as the interval between carcinogen treatment and surgery was increased.

Animals↗

PubMed2005

Structural changes of DNA induced by mono- and binuclear cancer drugs.

The structural features of the drug-DNA adducts resulted from treatment of DNA with the platinum based mononuclear drug cisplatin and the binuclear drug [{trans-PtCl(NH3)2}2H2N(CH2)4NH2]Cl2 or bis(platin) have been investigated by atomic force microscopy (AFM). Reduction in the contour length of the DNA fragments has been observed after cisplatin treatment while, compaction and aggregation are found to be the primary structural modifications following treatment with the binuclear drug. The intermolecular interaction upon bis(platin) treatment leads to observation of highly condense aggregates without a distinct sight of single isolated DNA molecule. These differences in drug binding indicate that unlike the mononuclear drug cisplatin, bis(platin) causes extensive interhelical/intermolecular cross-linking through its multiple linking sites. To our knowledge, this is the first report of a comparative AFM study to monitor the effects of a mono- and a binuclear platinum anti-cancer drug on DNA structure. These observations should provide clues towards explaining the distinct biological activities of the two drugs.

Aluminum Silicates↗

PubMed2005

Ligand exchange upon oxidation of a dinuclear Mn complex--detection of structural changes by FT-IR spectroscopy and ESI-MS.

The structural rearrangements triggered by oxidation of the dinuclear Mn complex [Mn(2)(bpmp)(mu-OAc)2]+(bpmp = 2,6-bis[bis(2-pyridylmethyl)amino]methyl-4-methylphenol anion) in the presence of water have been studied by combinations of electrochemistry with IR spectroscopy and with electrospray ionization mass spectrometry (ESI-MS). The exchange of acetate bridges for water (D2O) derived ligands in different oxidation states could be monitored by mid-IR spectroscopy in CD(3)CN-D(2)O mixtures following the v(as(C-O)) bands of bound acetate at 1594.4 cm(-1)(II,II), 1592.0 cm(-1)(II,III) and 1586.5 cm(-1)(III,III). Substantial loss of bound acetate occurs at much lower water content (< 0.5% v/v) in the III,III state than in the II,II and II,III states (> or = 10%). The ligand-exchange reactions do not initially reduce the overall charge of the complex but facilitate further oxidation by proton-coupled electron transfer as the water-derived ligands are increasingly deprotonated in higher oxidation states. In the IR spectra deprotonation could be followed by the formation of acetic acid (DOAc, approximately 1725 cm(-1), v(C-O)) from the released acetate (1573.6 cm(-1), v(as(C-O))). By the on-line combination of an electrochemical flow cell with ESI-MS several product complexes could be identified. A di-mu-oxo bridged III,IV dimer [Mn(2)(bpmp)(mu-O)(2)](2+)(m/z 335.8) can be generated at potentials below the III,III/II,III couple of the di-mu-acetato complex (0.61 V vs. ferrocene). The ligand-exchange reactions allow for three metal-centered oxidation steps to occur from II,II to III,IV in a potential range of only 0.5 V, explaining the formation of a spin-coupled III,IV dimer by photo-oxidation with [Ru[bpy)(3)](3+) in previous EPR studies.

Acetonitriles↗

PubMed2000

New insights in cardiac structural changes in patients with Fabry's disease.

BACKGROUND: Fabry's disease is an X-linked recessive genetic deficiency of the enzyme alpha-galactosidase leading to the pathologic intracellular deposition of neutral glycosphingolipids. Although cardiac involvement is frequent, there is controversy regarding the character of the associated left ventricular (LV) changes and the severity of valvular involvement. METHODS: Clinical evaluation (disease severity scaling, laboratory tests, and echocardiography) was performed in 13 hemizygous men (mean age 39 +/- 10 years) and 17 heterozygous women (mean age 35 +/- 19 years). RESULTS: LV hypertrophy (LVH) was frequent in subjects older than 30 years, more often in men (61%) than in women (18%, P <.001). The degree of LVH was independently associated with age and the logarithm of alpha-galactosidase activity (r(2) = 0.70, P <.001). The predominant LV geometric patterns were concentric LVH and remodeling, both present in 11 subjects (36%). Three patients had an asymmetric septal hypertrophy mimicking hypertrophic cardiomyopathy. In most subjects with LVH, the systolic function was normal and severe diastolic dysfunction (restrictive pattern) was not noted. Minor structural abnormalities of the mitral valve were found in 17 subjects (57%). The aortic valve was affected in 14 patients (47%). Valvular abnormalities were frequently accompanied by regurgitation of minor to mild degree. The presence of LVH or valvular changes was associated with increased disease severity. CONCLUSIONS: Echocardiographically detectable cardiac involvement is frequent with Fabry's disease, particularly in older subjects, and more pronounced in affected hemizygous men than in heterozygous women. LVH is frequently observed but usually not associated with significant systolic or restrictive diastolic dysfunction. Concentric LVH and remodeling appear to be the major manifestations of LV structural alteration. The frequently noted valvular abnormalities were not associated with a significant degree of regurgitation. Valvular and especially LV structural changes may serve as a useful marker of disease severity.

Adolescent↗

PubMed2005

Ca(2+)-regulated structural changes in troponin.

Troponin senses Ca2+ to regulate contraction in striated muscle. Structures of skeletal muscle troponin composed of TnC (the sensor), TnI (the regulator), and TnT (the link to the muscle thin filament) have been determined. The structure of troponin in the Ca(2+)-activated state features a nearly twofold symmetrical assembly of TnI and TnT subunits penetrated asymmetrically by the dumbbell-shaped TnC subunit. Ca ions are thought to regulate contraction by controlling the presentation to and withdrawal of the TnI inhibitory segment from the thin filament. Here, we show that the rigid central helix of the sensor binds the inhibitory segment of TnI in the Ca(2+)-activated state. Comparison of crystal structures of troponin in the Ca(2+)-activated state at 3.0 angstroms resolution and in the Ca(2+)-free state at 7.0 angstroms resolution shows that the long framework helices of TnI and TnT, presumed to be a Ca(2+)-independent structural domain of troponin are unchanged. Loss of Ca ions causes the rigid central helix of the sensor to collapse and to release the inhibitory segment of TnI. The inhibitory segment of TnI changes conformation from an extended loop in the presence of Ca2+ to a short alpha-helix in its absence. We also show that Anapoe, a detergent molecule, increases the contractile force of muscle fibers and binds specifically, together with the TnI switch helix, in a hydrophobic pocket of TnC upon activation by Ca ions.

Animals↗