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111.
Roderick A. Capaldi Robert Aggeler Stephan Wilkens Gerhard Grüber 《Journal of bioenergetics and biomembranes》1996,28(5):397-401
Structural changes in theEscherichia coli ATP synthase (ECF1F0) occur as part of catalysis, cooperativity and energy coupling within the complex. The and subunits, two major components of the stalk that links the F1 and F0 parts, are intimately involved in conformational coupling that links catalytic site events in the F1 part with proton pumping through the membrane embedded F0 sector. Movements of the subunit have been observed by electron microscopy, and by cross-linking and fluorescence studies in which reagents are bound to Cys residues introduced at selected sites by mutagenesis. Conformational changes and shifts of the subunit related to changes in nucleotide occupancy of catalytic sites have been followed by similar approaches. 相似文献
112.
Summary The evolution of disease resistance in plants may be constrained if genes conferring resistance to pathogens interfere with plant responses toward other, nonpathogenic organisms. To test for such effects, we compared symbiotic nitrogen fixation in Amphicarpaea bracteata plants that differed at a major locus controlling resistance to the pathogen Synchytrium decipiens. Both resistant and susceptible plant genotypes nodulated successfully and grew significantly better in the presence of Rhizobium, although growth enhancement by Rhizobium was altered by different levels of nitrate fertilization. Plants homozygous for disease resistance achieved 2% higher growth than susceptible homozygotes across all treatments, but this difference was not significant. Resistant and susceptible plant genotypes did not differ in the mean number of nodules formed per plant or in nodule diameter. However, there was highly significant variation among replicate families within each disease resistance category for both nodulation characteristics. These results imply that genetic variation exists among A. bracteata plants both for diease resistance and for traits affecting symbiotic nitrogen fixation. However, there were no evident pleiotropic effects of disease resistance genes on the plant-Rhizobium symbiosis. 相似文献
113.
Dopamine (DA) causes a dose-dependent increase in the frequency of motor neuron bursts [virtual ventilation (fR)] produced by deafferented crab ventilatory pattern generators (CPGv). Domperidone, a D2-specific DA antagonist, by itself reversibly depresses fR and also blocks the stimulatory effects of DA. Serotonin (5HT) has no direct effects on this CPGv. Nicotine also causes dramatic dose-dependent increases in the frequency of motor bursts from the CPGv. The action is triphasic, beginning with an initial reversal of burst pattern typical of reversed-mode ventilation, followed by a 2- to 3-min period of depression and then a long period of elevated burst rate. Acetylcholine chloride (ACh) alone is ineffective, but in the presence of eserine is moderately stimulatory. The inhibitory effects of nicotine are only partially blocked by curare. The excitatory action of nicotine is blocked by prior perfusion of domperidone, but not by SKF-83566.HCl, a D1-specific DA antagonist. SKF-83566 had no effects on the ongoing pattern of firing. These observations support the hypothesis that dopaminergic pathways are involved in the maintenance of the CPGv rhythm and that the acceleratory effects of nicotine may involve release of DA either directly or via stimulation of atypical ACh receptors at intraganglionic sites. © 1992 John Wiley & Sons, Inc. 相似文献
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116.
Vacuolar ATPases (V1V0 -ATPases) function in proton translocation across lipid membranes of subcellular compartments. We have used antibody labeling and electron microscopy to define the position of subunit C in the vacuolar ATPase from yeast. The data show that subunit C is binding at the interface of the ATPase and proton channel, opposite from another stalk density previously identified as subunit H [Wilkens S., Inoue T., and Forgac M. (2004) Three-dimensional structure of the vacuolar ATPase - Localization of subunit H by difference imaging and chemical cross-linking. J. Biol. Chem. 279, 41942-41949]. A picture of the vacuolar ATPase stalk domain is emerging in which subunits C and H are positioned to play a role in reversible enzyme dissociation and activity silencing. 相似文献
117.
Eukaryotic vacuolar ATPase (V-ATPase) is regulated by a reversible dissociation mechanism that involves breaking and reforming of protein-protein interactions at the interface of the V(1)-ATPase and V(o)-proton channel domains. We found previously that the head domain of the single copy C subunit (C(head)) binds one subunit EG heterodimer with high affinity (Oot, R.A. and Wilkens, S. (2010) J. Biol. Chem. 285, 24654-24664). Here we generated a water-soluble construct of the N-terminal domain of the V(o) "a" subunit composed of amino acid residues 104-372 (a(NT(104-372))). Analytical gel filtration chromatography and sedimentation velocity analysis revealed that a(NT(104-372)) undergoes reversible dimerization in a concentration-dependent manner. A low-resolution molecular envelope was calculated for the a(NT(104-372)) dimer using small angle x-ray scattering data. Isothermal titration calorimetry experiments revealed that a(NT(104-372)) binds the C(foot) and EG heterodimer with dissociation constants of 22 and 33 μM, respectively. We speculate that the spatial closeness of the a(NT), C(foot), and EG binding sites in the intact V-ATPase results in a high-avidity interaction that is able to resist the torque of rotational catalysis, and that reversible enzyme dissociation is initiated by breaking either the a(NT(104-372))-C(foot) or a(NT(104-372))-EG interaction by an as-yet unknown signaling mechanism. 相似文献
118.
Hansong Wang Christopher A. Haiman Laurence N. Kolonel Brian E. Henderson Lynne R. Wilkens Loïc Le Marchand Daniel O. Stram 《Human genetics》2010,128(2):165-177
It is well-known that population substructure may lead to confounding in case–control association studies. Here, we examined
genetic structure in a large racially and ethnically diverse sample consisting of five ethnic groups of the Multiethnic Cohort
study (African Americans, Japanese Americans, Latinos, European Americans and Native Hawaiians) using 2,509 SNPs distributed
across the genome. Principal component analysis on 6,213 study participants, 18 Native Americans and 11 HapMap III populations
revealed four important principal components (PCs): the first two separated Asians, Europeans and Africans, and the third
and fourth corresponded to Native American and Native Hawaiian (Polynesian) ancestry, respectively. Individual ethnic composition
derived from self-reported parental information matched well to genetic ancestry for Japanese and European Americans. STRUCTURE-estimated
individual ancestral proportions for African Americans and Latinos are consistent with previous reports. We quantified the
East Asian (mean 27%), European (mean 27%) and Polynesian (mean 46%) ancestral proportions for the first time, to our knowledge,
for Native Hawaiians. Simulations based on realistic settings of case–control studies nested in the Multiethnic Cohort found
that the effect of population stratification was modest and readily corrected by adjusting for race/ethnicity or by adjusting
for top PCs derived from all SNPs or from ancestry informative markers; the power of these approaches was similar when averaged
across causal variants simulated based on allele frequencies of the 2,509 genotyped markers. The bias may be large in case-only
analysis of gene by gene interactions but it can be corrected by top PCs derived from all SNPs. 相似文献
119.
Megan D. Fesinmeyer Kari E. North Marylyn D. Ritchie Unhee Lim Nora Franceschini Lynne R. Wilkens Myron D. Gross Petra Bůžková Kimberly Glenn P. Miguel Quibrera Lindsay Fernández‐Rhodes Qiong Li Jay H. Fowke Rongling Li Christopher S. Carlson Ross L. Prentice Lewis H. Kuller JoAnn E. Manson Tara C. Matise Shelley A. Cole Christina T.L. Chen Barbara V. Howard Laurence N. Kolonel Brian E. Henderson Kristine R. Monroe Dana C. Crawford Lucia A. Hindorff Steven Buyske Christopher A. Haiman Loic Le Marchand Ulrike Peters 《Obesity (Silver Spring, Md.)》2013,21(4):835-846
Objective:
Several genome–wide association studies (GWAS) have demonstrated that common genetic variants contribute to obesity. However, studies of this complex trait have focused on ancestrally European populations, despite the high prevalence of obesity in some minority groups.Design and Methods:
As part of the “Population Architecture using Genomics and Epidemiology (PAGE)” Consortium, we investigated the association between 13 GWAS‐identified single‐nucleotide polymorphisms (SNPs) and BMI and obesity in 69,775 subjects, including 6,149 American Indians, 15,415 African‐Americans, 2,438 East Asians, 7,346 Hispanics, 604 Pacific Islanders, and 37,823 European Americans. For the BMI‐increasing allele of each SNP, we calculated β coefficients using linear regression (for BMI) and risk estimates using logistic regression (for obesity defined as BMI ≥ 30) followed by fixed‐effects meta‐analysis to combine results across PAGE sites. Analyses stratified by racial/ethnic group assumed an additive genetic model and were adjusted for age, sex, and current smoking. We defined “replicating SNPs” (in European Americans) and “generalizing SNPs” (in other racial/ethnic groups) as those associated with an allele frequency‐specific increase in BMI.Results:
By this definition, we replicated 9/13 SNP associations (5 out of 8 loci) in European Americans. We also generalized 8/13 SNP associations (5/8 loci) in East Asians, 7/13 (5/8 loci) in African Americans, 6/13 (4/8 loci) in Hispanics, 5/8 in Pacific Islanders (5/8 loci), and 5/9 (4/8 loci) in American Indians.Conclusion:
Linkage disequilibrium patterns suggest that tagSNPs selected for European Americans may not adequately tag causal variants in other ancestry groups. Accordingly, fine‐mapping in large samples is needed to comprehensively explore these loci in diverse populations. 相似文献120.
Thuy La George Desmond Clark-Walker Xiaowen Wang Stephan Wilkens Xin Jie Chen 《Eukaryotic cell》2013,12(11):1451-1461
F1-ATPase is a rotary molecular machine with a subunit stoichiometry of α3β3γ1δ1ε1. It has a robust ATP-hydrolyzing activity due to effective cooperativity between the three catalytic sites. It is believed that the central γ rotor dictates the sequential conformational changes to the catalytic sites in the α3β3 core to achieve cooperativity. However, recent studies of the thermophilic Bacillus PS3 F1-ATPase have suggested that the α3β3 core can intrinsically undergo unidirectional cooperative catalysis (T. Uchihashi et al., Science 333:755-758, 2011). The mechanism of this γ-independent ATP-hydrolyzing mode is unclear. Here, a unique genetic screen allowed us to identify specific mutations in the α and β subunits that stimulate ATP hydrolysis by the mitochondrial F1-ATPase in the absence of γ. We found that the F446I mutation in the α subunit and G419D mutation in the β subunit suppress cell death by the loss of mitochondrial DNA (ρo) in a Kluyveromyces lactis mutant lacking γ. In organello ATPase assays showed that the mutant but not the wild-type γ-less F1 complexes retained 21.7 to 44.6% of the native F1-ATPase activity. The γ-less F1 subcomplex was assembled but was structurally and functionally labile in vitro. Phe446 in the α subunit and Gly419 in the β subunit are located on the N-terminal edge of the DELSEED loops in both subunits. Mutations in these two sites likely enhance the transmission of catalytically required conformational changes to an adjacent α or β subunit, thereby allowing robust ATP hydrolysis and cell survival under ρo conditions. This work may help our understanding of the structural elements required for ATP hydrolysis by the α3β3 subcomplex. 相似文献