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111.
The effects of several agents, sugars, isotonic KCl, and a variety of drugs, on the structure of the axonal membranes of unmyelinated pike olfactory nerve have been studied by synchrotron radiation X-ray scattering experiments. The main effects of the sugars are: (i) to increase the electron density of the extra-axonal space and thereby yield the absolute scale of the electron density profile; (ii) to osmotically stress the membrane and thus yield its elastic modulus of area compressibility, since the related strain, thickness dilation, is directly determined by the X-ray scattering experiments. Exposure to isotonic KCl, a depolarizing agent, induces membrane thickness to increase. The energy liberated in this process is a function of the amplitude of the dilation and of the elastic modulus of the membrane. This energy turns out to be close to the thermal energy liberated by the pike olfactory nerve during the initial phase of action potential that has previously been measured by others. Electrical depolarization thus seems to be accompanied by a thickness dilation of the axonal membrane. Another effect of isotonic KCl is to induce a large fraction of the membranes to pair by tight apposition of their extra-axonal faces. Local anaesthetics and some drugs have the effect of altering membrane thickness. All these observations are interpreted in terms of a modulation of the conformational disorder of the hydrocarbon chains of the lipid molecules. 相似文献
112.
Synchrotron radiation X-ray scattering experiments were performed on unmyelinated pike olfactory nerves. The difference between the meridional and the equatorial traces of the 2-D spectra yielded the 1-D equatorial intensity of the macromolecular components oriented with respect to the nerve: axonal membranes, microtubules and other cytoskeletal filaments. These 1-D spectra display a diffuse band typical of bilayer membranes and, at small s, a few sharper bands reminiscent of microtubules. All the spectra merge at large s. The intensity of the axonal membrane was determined via a noise analysis of the nerve-dependent spectra, involving also the notion that the thickness of the membrane is finite. The shape of the intensity function indicated that the electron density profile is not centrosymmetric. The knowledge of intensity and thickness paved the way to the electron density profile via an ab initio solution of the phase problem. An iterative procedure was adopted: (i) choose the lattice D of a 1-D pseudo crystal, interpolate the intensity at the points sh = h/D, adopt an arbitrary set of initial phases and compute the profile; (ii) determine the phases corresponding to this profile truncated by the thickness D/2; (iii) repeat the operation with the updated phases until a stable result is obtained. This iterative procedure was carried out for different D-values, starting in each case from randomly generated phases: stable results were obtained in less than 10,000 iterations. Most importantly, for D in the vicinity of 200 A, the overwhelming majority of the profiles were congruent with each other. These profiles were strongly asymmetric and otherwise typical of biological membranes. 相似文献
113.
Role of the microtubule destabilizing proteins SCG10 and stathmin in neuronal growth 总被引:7,自引:0,他引:7
The related proteins SCG10 and stathmin are highly expressed in the developing nervous system. Recently it was discovered that they are potent microtubule destabilizing factors. While stathmin is expressed in a variety of cell types and shows a cytosolic distribution, SCG10 is neuron-specific and membrane-associated. It contains an N-terminal targeting sequence that mediates its transport to the growing tips of axons and dendrites. SCG10 accumulates in the central domain of the growth cone, a region that also contains highly dynamic microtubules. These dynamic microtubules are known to be important for growth cone advance and responses to guidance cues. Because overexpression of SCG10 strongly enhances neurite outgrowth, SCG10 appears to be an important factor for the dynamic assembly and disassembly of growth cone microtubules during axonal elongation. Phosphorylation negatively regulates the microtubule destabilizing activity of SCG10 and stathmin, suggesting that these proteins may link extracellular signals to the rearrangement of the neuronal cytoskeleton. A role for these proteins in axonal elongation is also supported by their growth-associated expression pattern in nervous system development as well as during neuronal regeneration. 相似文献
114.
Kharat AS Coursange E Noirclerc-Savoye M Lacoste J Blot M 《Acta biochimica Polonica》2006,53(4):729-738
Transposition of insertion sequences (IS) is an enzyme-mediated process that only occurs in a minority of cells within a bacterial culture. Transposition is thus a rare event, but transposition frequency may vary depending on experimental conditions. For instance in a rich broth, IS elements are known to transpose during stationary phase but not during exponential growth. Using a reporter system which involves the activation of the cryptic bgl operon in Escherichia coli, we show that the frequency of IS1 transposition is a function of glucose concentration in the growth medium, it is increased by streptomycin amounts that are below minimum inhibitory concentration (sub-MIC) and is inhibited in an rpsL150 strain with high translation accuracy. Since starved cells are known to enhance ribosome frameshifting, our data suggests that growth conditions applied in this study could affect IS1 transposition by increasing translation infidelity. 相似文献
115.
Judith M. Rollinger Denise V. Kratschmar Daniela Schuster Petra H. Pfisterer Christel Gumy Evelyne M. Aubry Sarah Brandstötter Hermann Stuppner Gerhard Wolber Alex Odermatt 《Bioorganic & medicinal chemistry》2010,18(4):1507-1515
The inhibition of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), which catalyzes the conversion of inactive 11-ketoglucocorticoids to active 11β-hydroxyglucocorticoids, emerged as promising strategy to treat symptoms of the metabolic syndrome, including obesity and type 2 diabetes. In this study the leaves of the anti-diabetic medicinal plant loquat (Eriobotrya japonica) were phytochemically investigated following hints from a pharmacophore-based virtual screening and a bioactivity-guided approach. Determination of the 11β-HSD1 and 11β-HSD2 inhibitory activities in cell lysates revealed triterpenes from the ursane type as selective, low micro-molar inhibitors of 11β-HSD1, that is, corosolic acid (1), 3-epicorosolic acid methyl ester (4), 2-α hydroxy-3-oxo urs-12-en-28-oic acid (6), tormentic acid methyl ester (8), and ursolic acid (9). Importantly, a mixture of loquat constituents with moderate activities displayed a pronounced additive effect. By means of molecular modeling studies and the identification of the 11β-HSD1-inhibiting 11-keto-ursolic acid (17) and 3-acetyl-11-keto-ursolic acid (18) a structure–activity relationship was deduced for this group of pentacyclic triterpenes. The mechanism of action elucidated in the present work together with the previously determined pharmacological activities provides these natural products with an astonishing multi-targeted anti-diabetic profile. 相似文献
116.
Sam Schoenmakers Evelyne Wassenaar Joop S. E. Laven J. Anton Grootegoed Willy M. Baarends 《Chromosoma》2010,119(3):311-324
During male meiotic prophase in mammals, X and Y are in a largely unsynapsed configuration, which is thought to trigger meiotic
sex chromosome inactivation (MSCI). In avian species, females are ZW, and males ZZ. Although Z and W in chicken oocytes show
complete, largely heterologous synapsis, they too undergo MSCI, albeit only transiently. The W chromosome is already inactive
in early meiotic prophase, and inactive chromatin marks may spread on to the Z upon synapsis. Mammalian MSCI is considered
as a specialised form of the general meiotic silencing mechanism, named meiotic silencing of unsynapsed chromatin (MSUC).
Herein, we studied the avian form of MSUC, by analysing the behaviour of the peculiar germline restricted chromosome (GRC)
that is present as a single copy in zebra finch spermatocytes. In the female germline, this chromosome is present in two copies,
which normally synapse and recombine. In contrast, during male meiosis, the single GRC is always eliminated. We found that
the GRC in the male germline is silenced from early leptotene onwards, similar to the W chromosome in avian oocytes. The GRC
remains largely unsynapsed throughout meiotic prophase I, although patches of SYCP1 staining indicate that part of the GRC
may self-synapse. In addition, the GRC is largely devoid of meiotic double strand breaks. We observed a lack of the inner
centromere protein INCENP on the GRC and elimination of the GRC following metaphase I. Subsequently, the GRC forms a micronucleus
in which the DNA is fragmented. We conclude that in contrast to MSUC in mammals, meiotic silencing of this single chromosome
in the avian germline occurs prior to, and independent of DNA double strand breaks and chromosome pairing, hence we have named
this phenomenon meiotic silencing prior to synapsis (MSPS). 相似文献
117.
Ahmad I Hoessli DC Walker-Nasir E Choudhary MI Rafik SM Shakoori AR;Nasir-ud-Din 《Journal of cellular biochemistry》2006,99(3):706-718
Protein functions are determined by their three-dimensional structures and the folded 3-D structure is in turn governed by the primary structure and post-translational modifications the protein undergoes during synthesis and transport. Defining protein functions in vivo in the cellular and extracellular environments is made very difficult in the presence of other molecules. However, the modifications taking place during and after protein folding are determined by the modification potential of amino acids and not by the primary structure or sequence. These post-translational modifications, like phosphorylation and O-linked N-acetylglucosamine (O-GlcNAc) modifications, are dynamic and result in temporary conformational changes that regulate many functions of the protein. Computer-assisted studies can help determining protein functions by assessing the modification potentials of a given protein. Integrins are important membrane receptors involved in bi-directional (outside-in and inside-out) signaling events. The beta3 integrin family, including, alpha(IIb)beta3 and alpha(v)beta3, has been studied for its role in platelet aggregation during clot formation and clot retraction based on hydroxyl group modification by phosphate and GlcNAc on Ser, Thr, or Tyr and their interplay on Ser and Thr in the cytoplasmic domain of the beta3 subunit. An antagonistic role of phosphate and GlcNAc interplay at Thr758 for controlling both inside-out and outside-in signaling events is proposed. Additionally, interplay of GlcNAc and phosphate at Ser752 has been proposed to control activation and inactivation of integrin-associated Src kinases. This study describes the multifunctional behavior of integrins based on their modification potential at hydroxyl groups of amino acids as a source of interplay. 相似文献
118.
119.
HIV-1 Tat raises an adjuvant-free humoral immune response controlled by its core region and its ability to form cysteine-mediated oligomers 总被引:4,自引:0,他引:4
Kittiworakarn J Lecoq A Moine G Thai R Lajeunesse E Drevet P Vidaud C Ménez A Léonetti M 《The Journal of biological chemistry》2006,281(6):3105-3115
Proteins are poor immunogens that require an adjuvant to raise an immune response. Here we show that the human immunodeficiency virus, type 1 Tat protein possesses an autoadjuvant property, and we have identified the determinants and the molecular events that are associated with this unusual property. Using a series of chemically synthesized Tat101 derivatives, we show that the core region controls the autoadjuvant phenomenon independently of the B-cell recognition and T-cell stimulation that are associated with epitopes respectively located on the N-terminal region and the cysteine-rich region. We also show that cysteine-mediated oligomerization is a key molecular event of the adjuvant-free antibody response. In particular, a Tat dimer formed by the oxidation of two cysteine residues, at position 34 only, raises an adjuvant-free antibody response that is comparable with that observed with the wild-type protein. Unlike the parent protein, the Tat dimer has no transactivating activity and remains homogeneous for several weeks in solution. This construct might be of value for the design of an adjuvant-free Tat-based vaccine. Furthermore, we suggest that the specific autoadjuvanticity determinant of Tat could be used to provide other proteins with adjuvant-free immunogenicity. 相似文献
120.
Lotierzo M Raux E Tse Sum Bui B Goasdoue N Libot F Florentin D Warren MJ Marquet A 《Biochemistry》2006,45(40):12274-12281
Biotin synthase, a member of the "radical SAM" family, catalyzes the final step of the biotin biosynthetic pathway, namely, the insertion of a sulfur atom into dethiobiotin (DTB). The active form of the enzyme contains two iron-sulfur clusters, a [4Fe-4S](2+) cluster liganded by Cys-53, Cys-57, and Cys-60 and the S-adenosylmethionine (AdoMet or SAM) cosubstrate and a [2Fe-2S](2+) cluster liganded by Cys-97, Cys-128, Cys-188, and Arg-260. Single-point mutation of each of these six conserved cysteines produced inactive variants. In this work, mutants of other highly conserved residues from the Y(150)NHNLD motif are described. They have properties similar to those of the wild-type enzyme with respect to their cluster content and characteristics. For all of them, the as-isolated form, which contains an air-stable [2Fe-2S](2+) center, can additionally accommodate an air-sensitive [4Fe-4S](2+) center which is generated by incubation under anaerobic conditions with Fe(2+) and S(2-). Their spectroscopic properties are similar to those of the wild type. However, they are inactive, except the mutant H152A that exhibits a weak activity. We show that the mutants, inactive in producing biotin, are also unable to cleave AdoMet and to produce the deoxyadenosyl radical (AdoCH(2)(*)). In the case of H152A, a value of 5.5 +/- 0.4 is found for the 5'-deoxyadenosine (AdoCH(3)):biotin ratio, much higher than the value of 2.8 +/- 0.3 usually observed with the wild type. This reveals a greater contribution of the abortive process in which the AdoCH(2)(*) radical is quenched by hydrogen atoms from the protein or from some components of the system. Thus, in this case, the coupling between the production of AdoCH(2)(*) and its reaction with the hydrogen at C-6 and C-9 of DTB is less efficient than that in the wild type, probably because of geometry's perturbation within the active site. 相似文献