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31.
32.
Most sexually reproducing organisms have the ability to recognize individuals of the same species. In ascomycete fungi including yeasts, mating between cells of opposite mating type depends on the molecular recognition of two peptidyl mating pheromones by their corresponding G-protein coupled receptors (GPCRs). Although such pheromone/receptor systems are likely to function in both mate choice and prezygotic isolation, very few studies have focused on the stringency of pheromone receptors. The fission yeast Schizosaccharomyces pombe has two mating types, Plus (P) and Minus (M). Here, we investigated the stringency of the two GPCRs, Mam2 and Map3, for their respective pheromones, P-factor and M-factor, in fission yeast. First, we switched GPCRs between S. pombe and the closely related species Schizosaccharomyces octosporus, which showed that SoMam2 (Mam2 of S. octosporus) is partially functional in S. pombe, whereas SoMap3 (Map3 of S. octosporus) is not interchangeable. Next, we swapped individual domains of Mam2 and Map3 with the respective domains in SoMam2 and SoMap3, which revealed differences between the receptors both in the intracellular regions that regulate the downstream signaling of pheromones and in the activation by the pheromone. In particular, we demonstrated that two amino acid residues of Map3, F214 and F215, are key residues important for discrimination of closely related M-factors. Thus, the differences in these two GPCRs might reflect the significantly distinct stringency/flexibility of their respective pheromone/receptor systems; nevertheless, species-specific pheromone recognition remains incomplete. 相似文献
33.
Nakase Y Nakamura-Kubo M Ye Y Hirata A Shimoda C Nakamura T 《Molecular biology of the cell》2008,19(6):2476-2487
The spindle pole body (SPB) of Schizosaccharomyces pombe is required for assembly of the forespore membrane (FSM) during meiosis. Before de novo biogenesis of the FSM, the meiotic SPB forms outer plaques, an event referred to as SPB modification. A constitutive SPB component, Spo15, plays an indispensable role in SPB modification and sporulation. Here, we analyzed two sporulation-specific genes, spo13(+) and spo2(+), which are not required for progression of meiotic nuclear divisions, but are essential for sporulation. Spo13 is a 16-kDa coiled-coil protein, and Spo2 is a 15-kDa nonconserved protein. Both Spo13 and Spo2 specifically associated with the meiotic SPB. The respective deletion mutants are viable, but defective in SPB modification and in the onset of FSM formation. Spo13 and Spo2 localized on the cytoplasmic side of the SPB in close contact with the nascent FSM. Localization of Spo13 to the SPB was dependent on Spo15 and Spo2; that of Spo2 depended only on Spo15, suggesting that their recruitment to the SPB is strictly controlled. Spo2 physically associated with both Spo15 and Spo13, but Spo13 and Spo15 did not interact directly. Taken together, these observations indicate that Spo2 is recruited to the SPB during meiosis and then assists in the localization of Spo13 to the outer surface of the SPB. 相似文献
34.
Issei Tsukamoto Hiroyuki Koshio Masaya Orita Chikashi Saitoh Hiroko Yanai-Inamura Chika Kitada-Nozawa Eisaku Yamamoto Takeyuki Yatsu Shuichi Sakamoto Shin-ichi Tsukamoto 《Bioorganic & medicinal chemistry》2009,17(24):8161-8167
A series of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine-5-ylidene)acetamide derivatives were optimized to achieve potent agonistic activity, both in vitro and in vivo, for the arginine vasopressin V2 receptor, resulting in the eventual discovery of compound 1g. Molecular modeling of compound 1g with V2 receptor was also examined to evaluate the binding mode of this series of compounds. 相似文献
35.
Human RIF1 and protein phosphatase 1 stimulate DNA replication origin licensing but suppress origin activation
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Shin‐ichiro Hiraga Tony Ly Javier Garzón Zuzana Hořejší Yoshi‐nobu Ohkubo Akinori Endo Chikashi Obuse Simon J Boulton Angus I Lamond Anne D Donaldson 《EMBO reports》2017,18(3):403-419
The human RIF1 protein controls DNA replication, but the molecular mechanism is largely unknown. Here, we demonstrate that human RIF1 negatively regulates DNA replication by forming a complex with protein phosphatase 1 (PP1) that limits phosphorylation‐mediated activation of the MCM replicative helicase. We identify specific residues on four MCM helicase subunits that show hyperphosphorylation upon RIF1 depletion, with the regulatory N‐terminal domain of MCM4 being particularly strongly affected. In addition to this role in limiting origin activation, we discover an unexpected new role for human RIF1‐PP1 in mediating efficient origin licensing. Specifically, during the G1 phase of the cell cycle, RIF1‐PP1 protects the origin‐binding ORC1 protein from untimely phosphorylation and consequent degradation by the proteasome. Depletion of RIF1 or inhibition of PP1 destabilizes ORC1, thereby reducing origin licensing. Consistent with reduced origin licensing, RIF1‐depleted cells exhibit increased spacing between active origins. Human RIF1 therefore acts as a PP1‐targeting subunit that regulates DNA replication positively by stimulating the origin licensing step, and then negatively by counteracting replication origin activation. 相似文献
36.
The Na,K-ATPase belongs to the P-type ATPase family of primary active cation pumps. Metal fluorides like magnesium-, beryllium-, and aluminum fluoride act as phosphate analogues and inhibit P-type ATPases by interacting with the phosphorylation site, stabilizing conformations that are analogous to specific phosphoenzyme intermediates. Cardiotonic steroids like ouabain used in the treatment of congestive heart failure and arrhythmias specifically inhibit the Na,K-ATPase, and the detailed structure of the highly conserved binding site has recently been described by the crystal structure of the shark Na,K-ATPase in a state analogous to E2·2K(+)·P(i) with ouabain bound with apparently low affinity (1). In the present work inhibition, and subsequent reactivation by high Na(+), after treatment of shark Na,K-ATPase with various metal fluorides are characterized. Half-maximal inhibition of Na,K-ATPase activity by metal fluorides is in the micromolar range. The binding of cardiotonic steroids to the metal fluoride-stabilized enzyme forms was investigated using the fluorescent ouabain derivative 9-anthroyl ouabain and compared with binding to phosphorylated enzyme. The fastest binding was to the Be-fluoride stabilized enzyme suggesting a preformed ouabain binding cavity, in accord with results for Ca-ATPase where Be-fluoride stabilizes the E2-P ground state with an open luminal ion access pathway, which in Na,K-ATPase could be a passage for ouabain. The Be-fluoride stabilized enzyme conformation closely resembles the E2-P ground state according to proteinase K cleavage. Ouabain, but not its aglycone ouabagenin, prevented reactivation of this metal fluoride form by high Na(+) demonstrating the pivotal role of the sugar moiety in closing the extracellular cation pathway. 相似文献
37.
Summary Cells of the fission yeast Schizosaccharomyces pombe carrying the mei3 mutation are unable to initiate meiosis, being arrested before premeiotic DNA synthesis. A plasmid pDB(mei3)1 containing an 8.6 kilobases (kb) DNA insert which complemented mei3 mutations was isolated from an S. pombe genomic library constructed in the vector pDB248. A HindIII fragment of 2.6 kb subcloned in both orientations into pDB248 complemented the mei3 mutation. The plasmid was designated pDB(mei3)2. The 2.6 kb fragment ligated to the vector YIp32 was integrated into the S. pombe chromosome at the mei3 locus, indicating that the cloned DNA fragment contains the mei3 gene itself. Both pDB(mei3)1 and pDB(mei3)2 allowed partial recovery of meiotic and sporulation ability in mei1 mutants, suggesting a close relationship between the mei1 and mei3 genes. Northern blot analysis with pDB(mei3)2 as the probe indicated that the mei3 mRNA (1.3 kb in length) is more abundant in cells cultured in nitrogen-free sporulation medium than in nitrogen-rich growth medium. 相似文献
38.
39.
Akira Sakurai Saburo Tamura Naohiko Yanagishima Chikashi Shimoda 《Bioscience, biotechnology, and biochemistry》2013,77(1):255-256
Ten diether-type monoglycosyl and glycobiosyl glycerolipids, including 3-O-(4-O-β-D-galactopyranosyl-β-D-glucopyranosyl)-l,2,-di-O-n-tetradecyl-sn-glycerol, a synthetic analogue of lactosyl ceramide, were synthesized and their stereochemistry was assigned unambiguously by 13C NMR using the values of C-H one bond couplings. Their 13C NMR were further analysed to show the diagnostic α-effect of glycosylation in these compounds depending on the anomeric configuration of the glycosyl residue linked to C-3′-O atom. 相似文献
40.
Fujita Y Hayashi T Kiyomitsu T Toyoda Y Kokubu A Obuse C Yanagida M 《Developmental cell》2007,12(1):17-30
The centromere is the chromosomal site that joins to microtubules during mitosis for proper segregation. Determining the location of a centromere-specific histone H3 called CENP-A at the centromere is vital for understanding centromere structure and function. Here, we report the identification of three human proteins essential for centromere/kinetochore structure and function, hMis18alpha, hMis18beta, and M18BP1, the complex of which is accumulated specifically at the telophase-G1 centromere. We provide evidence that such centromeric localization of hMis18 is essential for the subsequent recruitment of de novo-synthesized CENP-A. If any of the three is knocked down by RNAi, centromere recruitment of newly synthesized CENP-A is rapidly abolished, followed by defects such as misaligned chromosomes, anaphase missegregation, and interphase micronuclei. Tricostatin A, an inhibitor to histone deacetylase, suppresses the loss of CENP-A recruitment to centromeres in hMis18alpha RNAi cells. Telophase centromere chromatin may be primed or licensed by the hMis18 complex and RbAp46/48 to recruit CENP-A through regulating the acetylation status in the centromere. 相似文献