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31.
32.
Pebay-Peyroula E Dahout-Gonzalez C Kahn R Trézéguet V Lauquin GJ Brandolin G 《Nature》2003,426(6962):39-44
ATP, the principal energy currency of the cell, fuels most biosynthetic reactions in the cytoplasm by its hydrolysis into ADP and inorganic phosphate. Because resynthesis of ATP occurs in the mitochondrial matrix, ATP is exported into the cytoplasm while ADP is imported into the matrix. The exchange is accomplished by a single protein, the ADP/ATP carrier. Here we have solved the bovine carrier structure at a resolution of 2.2 A by X-ray crystallography in complex with an inhibitor, carboxyatractyloside. Six alpha-helices form a compact transmembrane domain, which, at the surface towards the space between inner and outer mitochondrial membranes, reveals a deep depression. At its bottom, a hexapeptide carrying the signature of nucleotide carriers (RRRMMM) is located. Our structure, together with earlier biochemical results, suggests that transport substrates bind to the bottom of the cavity and that translocation results from a transient transition from a 'pit' to a 'channel' conformation. 相似文献
33.
Fischer J Lefèvre C Morava E Mussini JM Laforêt P Negre-Salvayre A Lathrop M Salvayre R 《Nature genetics》2007,39(1):28-30
Neutral lipid storage disease comprises a heterogeneous group of autosomal recessive disorders characterized by systemic accumulation of triglycerides in cytoplasmic droplets. Here we report a neutral lipid storage disease subgroup characterized by mild myopathy, absence of ichthyosis and mutations in both alleles of adipose triglyceride lipase (PNPLA2, also known as ATGL). Three of these mutations are predicted to lead to a truncated ATGL protein with an intact patatin domain containing the active site, but with defects in the hydrophobic domain. The block in triglyceride degradation was mimicked by short interfering RNA directed against ATGL. NLSDM is distinct from Chanarin-Dorfman syndrome, which is characterized by neutral lipid storage disease with ichthyosis, mild myopathy and hepatomegaly due to mutations in ABHD5 (also known as CGI-58). 相似文献
34.
Larsson P Oyston PC Chain P Chu MC Duffield M Fuxelius HH Garcia E Hälltorp G Johansson D Isherwood KE Karp PD Larsson E Liu Y Michell S Prior J Prior R Malfatti S Sjöstedt A Svensson K Thompson N Vergez L Wagg JK Wren BW Lindler LE Andersson SG Forsman M Titball RW 《Nature genetics》2005,37(2):153-159
Francisella tularensis is one of the most infectious human pathogens known. In the past, both the former Soviet Union and the US had programs to develop weapons containing the bacterium. We report the complete genome sequence of a highly virulent isolate of F. tularensis (1,892,819 bp). The sequence uncovers previously uncharacterized genes encoding type IV pili, a surface polysaccharide and iron-acquisition systems. Several virulence-associated genes were located in a putative pathogenicity island, which was duplicated in the genome. More than 10% of the putative coding sequences contained insertion-deletion or substitution mutations and seemed to be deteriorating. The genome is rich in IS elements, including IS630 Tc-1 mariner family transposons, which are not expected in a prokaryote. We used a computational method for predicting metabolic pathways and found an unexpectedly high proportion of disrupted pathways, explaining the fastidious nutritional requirements of the bacterium. The loss of biosynthetic pathways indicates that F. tularensis is an obligate host-dependent bacterium in its natural life cycle. Our results have implications for our understanding of how highly virulent human pathogens evolve and will expedite strategies to combat them. 相似文献
35.
Zusammenfassung Nachweis der endogenen Atmungsaktivierung von Mitochondrien im braunen Fettgewebe durch ATP und Karnitin. Eine maximale Aktivierung wird bei 6–30 Tage alten Ratten gefunden, während sie in neugeborenen und erwachsenen Tieren kleiner ist. Nur bei den 6–30 Tage alten Tieren hemmt Albumin die Durch ATP und Karnitin erhöhte Atmung. 相似文献
36.
Zusammenfassung Feststellung, dass die eindimensionale Diffusions-Methode eine sensitive, einfache und reproduzierbare Technik zur Bestimmung der Veränderungen der fibrinolytischen Aktivität bei Ratten ist. 相似文献
37.
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Capak PL Riechers D Scoville NZ Carilli C Cox P Neri R Robertson B Salvato M Schinnerer E Yan L Wilson GW Yun M Civano F Elvis M Karim A Mobasher B Staguhn JG 《Nature》2011,470(7333):233-235
Massive clusters of galaxies have been found that date from as early as 3.9 billion years (3.9 Gyr; z = 1.62) after the Big Bang, containing stars that formed at even earlier epochs. Cosmological simulations using the current cold dark matter model predict that these systems should descend from 'protoclusters'-early overdensities of massive galaxies that merge hierarchically to form a cluster. These protocluster regions themselves are built up hierarchically and so are expected to contain extremely massive galaxies that can be observed as luminous quasars and starbursts. Observational evidence for this picture, however, is sparse because high-redshift protoclusters are rare and difficult to observe. Here we report a protocluster region that dates from 1 Gyr (z = 5.3) after the Big Bang. This cluster of massive galaxies extends over more than 13 megaparsecs and contains a luminous quasar as well as a system rich in molecular gas. These massive galaxies place a lower limit of more than 4 × 10(11) solar masses of dark and luminous matter in this region, consistent with that expected from cosmological simulations for the earliest galaxy clusters. 相似文献
39.
Résumé On a obtenu 2 pools majeurs de-carotène dans l'homogénat du mycélium deB. trispora. L'un d'eux est associé à la fraction sédimentable à 4,900×g, l'autre aux globules de matière grasse, dans le cytoplasme. 相似文献
40.
All organisms have to monitor the folding state of cellular proteins precisely. The heat-shock protein DegP is a protein quality control factor in the bacterial envelope that is involved in eliminating misfolded proteins and in the biogenesis of outer-membrane proteins. Here we describe the molecular mechanisms underlying the regulated protease and chaperone function of DegP from Escherichia coli. We show that binding of misfolded proteins transforms hexameric DegP into large, catalytically active 12-meric and 24-meric multimers. A structural analysis of these particles revealed that DegP represents a protein packaging device whose central compartment is adaptable to the size and concentration of substrate. Moreover, the inner cavity serves antagonistic functions. Whereas the encapsulation of folded protomers of outer-membrane proteins is protective and might allow safe transit through the periplasm, misfolded proteins are eliminated in the molecular reaction chamber. Oligomer reassembly and concomitant activation on substrate binding may also be critical in regulating other HtrA proteases implicated in protein-folding diseases. 相似文献