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21.
Della Valle MC Sleat DE Zheng H Moore DF Jadot M Lobel P 《Molecular & cellular proteomics : MCP》2011,10(4):M110.006403
One approach to the functional characterization of the lysosome lies in the use of proteomic methods to identify proteins in subcellular fractions enriched for this organelle. However, distinguishing between true lysosomal residents and proteins from other cofractionating organelles is challenging. To this end, we implemented a quantitative mass spectrometry approach based on the selective decrease in the buoyant density of liver lysosomes that occurs when animals are treated with Triton-WR1339. Liver lysosome-enriched preparations from control and treated rats were fractionated by isopycnic sucrose density gradient centrifugation. Tryptic peptides derived from gradient fractions were reacted with isobaric tag for relative and absolute quantitation eight-plex labeling reagents and analyzed by two-dimensional liquid chromatography matrix-assisted laser desorption ionization time-of-flight MS. Reporter ion intensities were used to generate relative protein distribution profiles across both types of gradients. A distribution index was calculated for each identified protein and used to determine a probability of lysosomal residence by quadratic discriminant analysis. This analysis suggests that several proteins assigned to the lysosome in other proteomics studies are not true lysosomal residents. Conversely, results support lysosomal residency for other proteins that are either not or only tentatively assigned to this location. The density shift for two proteins, Cu/Zn superoxide dismutase and ATP-binding cassette subfamily B (MDR/TAP) member 6, was corroborated by quantitative Western blotting. Additional balance sheet analyses on differential centrifugation fractions revealed that Cu/Zn superoxide dismutase is predominantly cytosolic with a secondary lysosomal localization whereas ATP-binding cassette subfamily B (MDR/TAP) member 6 is predominantly lysosomal. These results establish a quantitative mass spectrometric/subcellular fractionation approach for identification of lysosomal proteins and underscore the necessity of balance sheet analysis for localization studies. 相似文献
22.
Giorgio M Trinei M Migliaccio E Pelicci PG 《Nature reviews. Molecular cell biology》2007,8(9):722-728
The reactive oxygen species that are generated by mitochondrial respiration, including hydrogen peroxide (H2O2), are potent inducers of oxidative damage and mediators of ageing. It is not clear, however, whether oxidative stress is the result of a genetic programme or the by-product of physiological processes. Recent findings demonstrate that a fraction of mitochondrial H2O2, produced by a specialized enzyme as a signalling molecule in the pathway of apoptosis, induces intracellular oxidative stress and accelerates ageing. We propose that genes that control H2O2 production are selected determinants of lifespan. 相似文献
23.
Lan YY Wang Z Raimondi G Wu W Colvin BL de Creus A Thomson AW 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(9):5868-5877
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Bisetto E Picotti P Giorgio V Alverdi V Mavelli I Lippe G 《Journal of bioenergetics and biomembranes》2008,40(4):257-267
The role of the integral inner membrane subunit e in self-association of F0F1ATP synthase from bovine heart mitochondria was analyzed by in situ limited proteolysis, blue native PAGE/iterative SDS-PAGE, and LC-MS/MS. Selective degradation of subunit e, without disrupting
membrane integrity or ATPase capacity, altered the oligomeric distribution of F0F1ATP synthase, by eliminating oligomers and reducing dimers in favor of monomers. The stoichiometry of subunit e was determined
by a quantitative MS-based proteomics approach, using synthetic isotope-labelled reference peptides IAQL*EEVK, VYGVGSL*ALYEK,
and ELAEAQEDTIL*K to quantify the b, γ and e subunits, respectively. Accuracy of the method was demonstrated by confirming
the 1:1 stoichiometry of subunits γ and b. Altogether, the results indicate that the integrity of a unique copy of subunit
e is essential for self-association of mammalian F0F1ATP synthase.
Elena Bisetto and Paola Picotti contributed equally to this work. 相似文献
26.
UTRdb and UTRsite: specialized databases of sequences and functional elements of 5′ and 3′ untranslated regions of eukaryotic mRNAs. Update 2002 下载免费PDF全文
27.
Cavallini G Crippa A Magli MC Cavallini N Ferraretti AP Gianaroli L 《Biology of reproduction》2008,79(4):667-673
Interdependence between sperm concentration, motility, morphology, and the percentage of aneuploid sperm was explored to test whether oligoasthenoteratospermia (OAT) may have a multiple origin in idiopathic infertile males. A total of 174 men (age, 35.8 +/- 4.3 yr) with idiopathic infertility were studied. Seven patients had nonobstructive azoospermia, 55 had severe OAT, 30 had OAT, 27 had isolated alterations of motility, 45 had alterations of morphology and of motility, and 10 had isolated alterations of morphology. The sperm morphology was assessed with strict criteria. The percentage of aneuploid sperm was assessed with fluorescent in situ hybridization for chromosomes X, Y, 13, 15, 16, 17, 18, 21, and 22. Relationships between sperm features, and the relationship between sperm features and aneuploidies were analyzed with multivariate regression analysis. Statistical analysis did not find any significant relationship between the percentage of typical forms and sperm concentration or between morphology and motility. On the other hand, a positive and significant relationship was found between sperm concentration and motility. The percentage of aneuploid sperm was inversely and significantly related to the percentage of typical forms but not to motility and concentration. Sperm morphology is an independent characteristic with respect to concentration and motility, whereas it showed a significant inverse relationship with respect to the percentage of aneuploid sperm. This means that idiopathic OAT may occur by means of at least two independent pathways, the first affecting concentration and/or motility and the second affecting morphology. 相似文献
28.
Fabio Moda Chiara Vimercati Ilaria Campagnani Margherita Ruggerone Giorgio Giaccone Michela Morbin Lorena Zentilin Mauro Giacca Ileana Zucca Giuseppe Legname Fabrizio Tagliavini 《朊病毒》2012,6(4):383-390
Prion diseases are caused by a conformational modification of the cellular prion protein (PrPC) into disease-specific forms, termed PrPSc, that have the ability to interact with PrPC promoting its conversion to PrPSc. In vitro studies demonstrated that anti-PrP antibodies inhibit this process. In particular, the single chain variable fragment D18 antibody (scFvD18) showed high efficiency in curing chronically prion-infected cells. This molecule binds the PrPC region involved in the interaction with PrPSc thus halting further prion formation. These findings prompted us to test the efficiency of scFvD18 in vivo. A recombinant Adeno-Associated Viral vector serotype 9 was used to deliver scFvD18 to the brain of mice that were subsequently infected by intraperitoneal route with the mouse-adapted scrapie strain RML. We found that the treatment was safe, prolonged the incubation time of scrapie-infected animals and decreased the burden of total proteinase-resistant PrPSc in the brain, suggesting that scFvD18 interferes with prion replication in vivo. This approach is relevant for designing new therapeutic strategies for prion diseases and other disorders characterized by protein misfolding. 相似文献
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30.
Federica Chiappori Ivan Merelli Giorgio Colombo Luciano Milanesi Giulia Morra 《PLoS computational biology》2012,8(12)
Investigating ligand-regulated allosteric coupling between protein domains is fundamental to understand cell-life regulation. The Hsp70 family of chaperones represents an example of proteins in which ATP binding and hydrolysis at the Nucleotide Binding Domain (NBD) modulate substrate recognition at the Substrate Binding Domain (SBD). Herein, a comparative analysis of an allosteric (Hsp70-DnaK) and a non-allosteric structural homolog (Hsp110-Sse1) of the Hsp70 family is carried out through molecular dynamics simulations, starting from different conformations and ligand-states. Analysis of ligand-dependent modulation of internal fluctuations and local deformation patterns highlights the structural and dynamical changes occurring at residue level upon ATP-ADP exchange, which are connected to the conformational transition between closed and open structures. By identifying the dynamically responsive protein regions and specific cross-domain hydrogen-bonding patterns that differentiate Hsp70 from Hsp110 as a function of the nucleotide, we propose a molecular mechanism for the allosteric signal propagation of the ATP-encoded conformational signal. 相似文献