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排序方式: 共有797条查询结果,搜索用时 9 毫秒
191.
Masashi Shingai Sarah Welbourn Jason M. Brenchley Priyamvada Acharya Eri Miyagi Ronald J. Plishka Alicia Buckler-White Peter D. Kwong Yoshiaki Nishimura Klaus Strebel Malcolm A. Martin 《PLoS pathogens》2015,11(5)
For nearly 20 years, the principal biological function of the HIV-2/SIV Vpx gene has been thought to be required for optimal virus replication in myeloid cells. Mechanistically, this Vpx activity was recently reported to involve the degradation of Sterile Alpha Motif and HD domain-containing protein 1 (SAMHD1) in this cell lineage. Here we show that when macaques were inoculated with either the T cell tropic SIVmac239 or the macrophage tropic SIVmac316 carrying a Vpx point mutation that abrogates the recruitment of DCAF1 and the ensuing degradation of endogenous SAMHD1 in cultured CD4+ T cells, virus acquisition, progeny virion production in memory CD4+ T cells during acute infection, and the maintenance of set-point viremia were greatly attenuated. Revertant viruses emerging in two animals exhibited an augmented replication phenotype in memory CD4+ T lymphocytes both in vitro and in vivo, which was associated with reduced levels of endogenous SAMHD1. These results indicate that a critical role of Vpx in vivo is to promote the degradation of SAMHD1 in memory CD4+ T lymphocytes, thereby generating high levels of plasma viremia and the induction of immunodeficiency. 相似文献
192.
193.
Lapinsky DJ Aggarwal S Nolan TL Surratt CK Lever JR Acharya R Vaughan RA Pandhare A Blanton MP 《Bioorganic & medicinal chemistry letters》2012,22(1):523-526
Towards addressing the knowledge gap of how bupropion interacts with the dopamine transporter (DAT) and nicotinic acetylcholine receptors (nAChRs), a ligand was synthesized in which the chlorine of bupropion was isosterically replaced with an iodine and a photoreactive azide was added to the 4'-position of the aromatic ring. Analog (±)-3 (SADU-3-72) demonstrated modest DAT and α4β2 nAChR affinity. A radioiodinated version was shown to bind covalently to hDAT expressed in cultured cells and affinity-purified, lipid-reincorporated human α4β2 neuronal nAChRs. Co-incubation of (±)-[(125)I]-3 with non-radioactive (±)-bupropion or (-)-cocaine blocked labeling of these proteins. Compound (±)-[(125)I]-3 represents the first successful example of a DAT and nAChR photoaffinity ligand based on the bupropion scaffold. Such ligands are expected to assist in mapping bupropion-binding pockets within plasma membrane monoamine transporters and ligand-gated nAChR ion channels. 相似文献
194.
Corradi HR Corrigall AV Boix E Mohan CG Sturrock ED Meissner PN Acharya KR 《The Journal of biological chemistry》2006,281(50):38625-38633
Protoporphyrinogen IX oxidase, a monotopic membrane protein, which catalyzes the oxidation of protoporphyrinogen IX to protoporphyrin IX in the heme/chlorophyll biosynthetic pathway, is distributed widely throughout nature. Here we present the structure of protoporphyrinogen IX oxidase from Myxococcus xanthus, an enzyme with similar catalytic properties to human protoporphyrinogen IX oxidase that also binds the common plant herbicide, acifluorfen. In the native structure, the planar porphyrinogen substrate is mimicked by a Tween 20 molecule, tracing three sides of the macrocycle. In contrast, acifluorfen does not mimic the planarity of the substrate but is accommodated by the shape of the binding pocket and held in place by electrostatic and aromatic interactions. A hydrophobic patch surrounded by positively charged residues suggests the position of the membrane anchor, differing from the one proposed for the tobacco mitochondrial protoporphyrinogen oxidase. Interestingly, there is a discrepancy between the dimerization state of the protein in solution and in the crystal. Conserved structural features are discussed in relation to a number of South African variegate porphyria-causing mutations in the human enzyme. 相似文献
195.
We present the thermal stability monitored by circular dichroism (CD) spectroscopy at 222 nm of 100 heterodimers that contain all possible coiled-coil a-a' pairs for 10 amino acids (I, V, L, N, A, K S, T, E, and R). This includes the stability of 36 heterodimers for 6 amino acids (I, V, L, N, A, and K) previously described and 64 new heterodimers including the 4 amino acids (S, T, E, and R). We have calculated a double mutant alanine thermodynamic cycle to determine a-a' pair coupling energies to evaluate which a-a' pairs encourage specific dimerization partners. The four new homotypic a-a' pairs (T-T, S-S, R-R, E-E) are repulsive relative to A-A and have destabilizing coupling energies. Among the 90 heterotypic a-a' pairs, the stabilizing coupling energies contain lysine or arginine paired with either an aliphatic or a polar amino acid. The range in coupling energies for each amino acid reveals its potential to regulate dimerization specificity. The a-a' pairs containing isoleucine and asparagine have the greatest range in coupling energies and thus contribute dramatically to dimerization specificity, which is to encourage homodimerization. In contrast, the a-a' pairs containing charged amino acids (K, R, and E) show the least range in coupling energies and promiscuously encourage heterodimerization. 相似文献
196.
In bovines characterization of biochemical and molecular determinants of the dominant follicle before and during different time intervals after gonadotrophin surge requires precise identification of the dominant follicle from a follicular wave. The objectives of the present study were to standardize an experimental model in buffalo cows for accurately identifying the dominant follicle of the first wave of follicular growth and characterize changes in follicular fluid hormone concentrations as well as expression patterns of various genes associated with the process of ovulation. From the day of estrus (day 0), animals were subjected to blood sampling and ultrasonography for monitoring circulating progesterone levels and follicular growth. On day 7 of the cycle, animals were administered a PGF(2alpha) analogue (Tiaprost Trometamol, 750 microg i.m.) followed by an injection of hCG (2000 IU i.m.) 36 h later. Circulating progesterone levels progressively increased from day 1 of the cycle to 2.26+/-0.17 ng/ml on day 7 of the cycle, but declined significantly after PGF(2alpha) injection. A progressive increase in the size of the dominant follicle was observed by ultrasonography. The follicular fluid estradiol and progesterone concentrations in the dominant follicle were 600+/-16.7 and 38+/-7.6 ng/ml, respectively, before hCG injection and the concentration of estradiol decreased to 125.8+/-25.26 ng/ml, but concentration of progesterone increased to 195+/-24.6 ng/ml, 24h post-hCG injection. Inh-alpha and Cyp19A1 expressions in granulosa cells were maximal in the dominant follicle and declined in response to hCG treatment. Progesterone receptor, oxytocin and cycloxygenase-2 expressions in granulosa cells, regarded as markers of ovulation, were maximal at 24h post-hCG. The expressions of genes belonging to the super family of proteases were also examined; Cathepsin L expression decreased, while ADAMTS 3 and 5 expressions increased 24h post-hCG treatment. The results of the current study indicate that sequential treatments of PGF(2alpha) and hCG during early estrous cycle in the buffalo cow leads to follicular growth that culminates in ovulation. The model system reported in the present study would be valuable for examining temporo-spatial changes in the periovulatory follicle immediately before and after the onset of gonadotrophin surge. 相似文献
197.
Alexander M. Many Christina S. Melki Oleksandr P. Savytskyy Daniel S. Maillet Sonia N. Acharya Miriam E. Zolan 《Chromosoma》2009,118(4):471-486
The Mre11-Rad50-Nbs1 (MRN) complex is required for numerous cellular processes that involve interactions with DNA double-strand
breaks. For the majority of these processes, the MRN complex is thought to act as a unit, with each protein aiding the activity
of the others. We have examined the relationship between Mre11 and Rad50 during meiosis in the basidiomycete Coprinus cinereus (Coprinopsis cinerea), investigating to what extent activities of Mre11 and Rad50 are interdependent. We showed that mre11-1 is epistatic to rad50-1 with respect to the time of meiotic arrest, indicating that Mre11 activity facilitates the diffuse diplotene arrest of rad50 mutants. Anti-Mre11 and anti-Rad50 antibodies were used to examine MRN complex localization in a wild-type strain and in
spo11, mre11, and rad50 mutants. In wild type, numbers of Mre11 and Rad50 foci peaked at time points corresponding to leptotene and early zygotene.
In the spo11-1 mutant, which is defective in meiotic double-strand break formation, foci accumulated throughout prophase I. Of seven MRN
mutants examined, only two rad50 strains exhibited Mre11 and Rad50 foci that localized to chromatin, although Mre11 protein was found in the cell for all
of them. Analysis of predicted mutant structures showed that stable localization of Mre11 and Rad50 does not depend upon a
wild-type hook-proximal coiled coil, but does require the presence of the Rad50 ATPase/adenylate cyclase domains. We found
that Mre11 and Rad50 were interdependent for binding to meiotic chromosomes. However, the majority of foci observed apparently
contained only one of the two proteins. Independent Mre11 and Rad50 foci might indicate disassociation of the complex during
meiosis or could reflect independent structural roles for the two proteins in meiotic chromatin.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
198.
Haryati Jamaluddin Percy Tumbale Tyrone A. Ferns Keith Brew K. Ravi Acharya 《Biochemical and biophysical research communications》2009,385(4):601-604
The specificities of glycosyltransferases make them useful for the synthesis of biologically active oligosaccharides, but also restrict their range of products. In substrate engineering, substrate promiscuity is enhanced by attaching removable interactive groups to weak substrates. Thus, the attachment of β p-nitrophenyl converts galactose from a poor into a good substrate of α-1,3-galactosyltransferase. The crystallographic structure of a complex of α3GT containing p-nitrophenyl-β-galactoside shows that the p-nitrophenyl binds similarly to the N-acetylglucosamine of the substrate, N-acetyllactosamine, interacting with the indole of Trp249. p-Nitrophenyl, unlike N-acetylglucosamine, makes no H-bonds but has more non-polar interactions, making it an effective monosaccharide mimetic. 相似文献
199.
Mitochondrial degeneration and not apoptosis is the primary cause of embryonic lethality in ceramide transfer protein mutant mice 总被引:3,自引:0,他引:3
Xin Wang Raghavendra Pralhada Rao Teresa Kosakowska-Cholody M. Athar Masood Eileen Southon Helin Zhang Cyril Berthet Kunio Nagashim Timothy K. Veenstra Lino Tessarollo Usha Acharya Jairaj K. Acharya 《The Journal of cell biology》2009,184(1):143-158
Ceramide transfer protein (CERT) functions in the transfer of ceramide from the endoplasmic reticulum (ER) to the Golgi. In this study, we show that CERT is an essential gene for mouse development and embryonic survival and, quite strikingly, is critical for mitochondrial integrity. CERT mutant embryos accumulate ceramide in the ER but also mislocalize ceramide to the mitochondria, compromising their function. Cells in mutant embryos show abnormal dilation of the ER and degenerating mitochondria. These subcellular changes manifest as heart defects and cause severely compromised cardiac function and embryonic death around embryonic day 11.5. In spite of ceramide accumulation, CERT mutant mice do not die as a result of enhanced apoptosis. Instead, cell proliferation is impaired, and expression levels of cell cycle–associated proteins are altered. Individual cells survive, perhaps because cell survival mechanisms are activated. Thus, global compromise of ER and mitochondrial integrity caused by ceramide accumulation in CERT mutant mice primarily affects organogenesis rather than causing cell death via apoptotic pathways. 相似文献
200.
Research in recent years on the biology of guard cells has shown that these specialized cells integrate both extra- and intra-cellular
signals in the control of stomatal apertures. Among the phytohormones, abscisic acid (ABA) is one of the key players regulating
stomatal function. In addition, auxin, cytokinin, ethylene, brassinosteroids, jasmonates, and salicylic acid also contribute
to stomatal aperture regulation. The interaction of multiple hormones can serve to determine the size of stomatal apertures
in a condition-specific manner. Here, we discuss the roles of different phytohormones and the effects of their interactions
on guard cell physiology and function. 相似文献