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  • Articles  (135)
  • Nature  (5)
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  • 1
    Publication Date: 1979-06-01
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 2
    Publication Date: 2020-07-01
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 3
    Publication Date: 2019
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 4
    Publication Date: 2019
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2010-02-19
    Description: E1 enzymes activate ubiquitin (Ub) and ubiquitin-like (Ubl) proteins in two steps by carboxy-terminal adenylation and thioester bond formation to a conserved catalytic cysteine in the E1 Cys domain. The structural basis for these intermediates remains unknown. Here we report crystal structures for human SUMO E1 in complex with SUMO adenylate and tetrahedral intermediate analogues at 2.45 and 2.6 A, respectively. These structures show that side chain contacts to ATP.Mg are released after adenylation to facilitate a 130 degree rotation of the Cys domain during thioester bond formation that is accompanied by remodelling of key structural elements including the helix that contains the E1 catalytic cysteine, the crossover and re-entry loops, and refolding of two helices that are required for adenylation. These changes displace side chains required for adenylation with side chains required for thioester bond formation. Mutational and biochemical analyses indicate these mechanisms are conserved in other E1s.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866016/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866016/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olsen, Shaun K -- Capili, Allan D -- Lu, Xuequan -- Tan, Derek S -- Lima, Christopher D -- F32 GM075695/GM/NIGMS NIH HHS/ -- F32 GM075695-03/GM/NIGMS NIH HHS/ -- R01 AI068038/AI/NIAID NIH HHS/ -- R01 AI068038-02/AI/NIAID NIH HHS/ -- R01 AI068038-03/AI/NIAID NIH HHS/ -- R01 GM065872/GM/NIGMS NIH HHS/ -- R01 GM065872-09/GM/NIGMS NIH HHS/ -- RR-15301/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Feb 18;463(7283):906-12. doi: 10.1038/nature08765.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology, Sloan-Kettering Institute, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20164921" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; *Biocatalysis ; Catalytic Domain/*physiology ; Conserved Sequence ; Crystallography, X-Ray ; Cysteine/chemistry/metabolism ; Humans ; Magnesium/metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; SUMO-1 Protein/*chemistry/*metabolism ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae Proteins/metabolism ; Small Ubiquitin-Related Modifier Proteins/metabolism ; Sulfides/*metabolism ; Ubiquitin/metabolism ; Ubiquitin-Activating Enzymes/*chemistry/*metabolism ; Ubiquitins/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2008-09-30
    Description: Mass spectrometry is a powerful technology for the analysis of large numbers of endogenous proteins. However, the analytical challenges associated with comprehensive identification and relative quantification of cellular proteomes have so far appeared to be insurmountable. Here, using advances in computational proteomics, instrument performance and sample preparation strategies, we compare protein levels of essentially all endogenous proteins in haploid yeast cells to their diploid counterparts. Our analysis spans more than four orders of magnitude in protein abundance with no discrimination against membrane or low level regulatory proteins. Stable-isotope labelling by amino acids in cell culture (SILAC) quantification was very accurate across the proteome, as demonstrated by one-to-one ratios of most yeast proteins. Key members of the pheromone pathway were specific to haploid yeast but others were unaltered, suggesting an efficient control mechanism of the mating response. Several retrotransposon-associated proteins were specific to haploid yeast. Gene ontology analysis pinpointed a significant change for cell wall components in agreement with geometrical considerations: diploid cells have twice the volume but not twice the surface area of haploid cells. Transcriptome levels agreed poorly with proteome changes overall. However, after filtering out low confidence microarray measurements, messenger RNA changes and SILAC ratios correlated very well for pheromone pathway components. Systems-wide, precise quantification directly at the protein level opens up new perspectives in post-genomics and systems biology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Godoy, Lyris M F -- Olsen, Jesper V -- Cox, Jurgen -- Nielsen, Michael L -- Hubner, Nina C -- Frohlich, Florian -- Walther, Tobias C -- Mann, Matthias -- England -- Nature. 2008 Oct 30;455(7217):1251-4. doi: 10.1038/nature07341. Epub 2008 Sep 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Proteomics and Signal Transduction, Max-Planck-Institute for Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18820680" target="_blank"〉PubMed〈/a〉
    Keywords: *Diploidy ; Gene Expression Profiling ; Genes, Fungal/genetics ; *Haploidy ; Mass Spectrometry/*methods ; Oligonucleotide Array Sequence Analysis ; Open Reading Frames ; Proteome/*analysis/genetics ; Proteomics/*methods ; RNA, Fungal/analysis/genetics ; Retroelements/genetics ; Saccharomyces cerevisiae/cytology/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/*analysis/genetics ; Staining and Labeling ; Transcription, Genetic/genetics
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  • 7
    Publication Date: 2008-09-27
    Description: Across the Greenland-Scotland ridge there is a continuous flow of cold dense water, termed 'overflow', from the Nordic seas to the Atlantic Ocean. This is a main contributor to the production of North Atlantic Deep Water that feeds the lower limb of the Atlantic meridional overturning circulation, which has been predicted to weaken as a consequence of climate change. The two main overflow branches pass the Denmark Strait and the Faroe Bank channel. Here we combine results from direct current measurements in the Faroe Bank channel for 1995-2005 with an ensemble hindcast experiment for 1948-2005 using an ocean general circulation model. For the overlapping period we find a convincing agreement between model simulations and observations on monthly to interannual timescales. Both observations and model data show no significant trend in volume transport. In addition, for the whole 1948-2005 period, the model indicates no persistent trend in the Faroe Bank channel overflow or in the total overflow transport, in agreement with the few available historical observations. Deepening isopycnals in the Norwegian Sea have tended to decrease the pressure difference across the Greenland-Scotland ridge, but this has been compensated for by the effect of changes in sea level. In contrast with earlier studies, we therefore conclude that the Faroe Bank channel overflow, and also the total overflow, did not decrease consistently from 1950 to 2005, although the model does show a weakening total Atlantic meridional overturning circulation as a result of changes south of the Greenland-Scotland ridge.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olsen, Steffen M -- Hansen, Bogi -- Quadfasel, Detlef -- Osterhus, Svein -- England -- Nature. 2008 Sep 25;455(7212):519-22. doi: 10.1038/nature07302.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Danish Meteorological Institute, Lyngbyvej 100, 2100 Copenhagen, Denmark. smo@dmi.dk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18818655" target="_blank"〉PubMed〈/a〉
    Keywords: Atlantic Ocean ; Computer Simulation ; Denmark ; Greenhouse Effect ; Greenland ; History, 20th Century ; History, 21st Century ; Ice/analysis ; Models, Theoretical ; Pressure ; Scotland ; Seawater/*analysis ; *Water Movements
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  • 8
    Publication Date: 2008-03-18
    Description: Olfactory signals are transduced by a large family of odorant receptor proteins, each of which corresponds to a unique glomerulus in the first olfactory relay of the brain. Crosstalk between glomeruli has been proposed to be important in olfactory processing, but it is not clear how these interactions shape the odour responses of second-order neurons. In the Drosophila antennal lobe (a region analogous to the vertebrate olfactory bulb), we selectively removed most interglomerular input to genetically identified second-order olfactory neurons. Here we show that this broadens the odour tuning of these neurons, implying that interglomerular inhibition dominates over interglomerular excitation. The strength of this inhibitory signal scales with total feedforward input to the entire antennal lobe, and has similar tuning in different glomeruli. A substantial portion of this interglomerular inhibition acts at a presynaptic locus, and our results imply that this is mediated by both ionotropic and metabotropic receptors on the same nerve terminal.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824883/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824883/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olsen, Shawn R -- Wilson, Rachel I -- R01 DC008174/DC/NIDCD NIH HHS/ -- R01 DC008174-03/DC/NIDCD NIH HHS/ -- England -- Nature. 2008 Apr 24;452(7190):956-60. doi: 10.1038/nature06864. Epub 2008 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18344978" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Drosophila melanogaster/*physiology ; Excitatory Postsynaptic Potentials/drug effects ; GABA-B Receptor Antagonists ; Neurons/drug effects/metabolism ; Odors/analysis ; Olfactory Pathways/drug effects/*physiology ; Patch-Clamp Techniques ; Physical Stimulation ; Presynaptic Terminals/drug effects/*physiology ; Receptors, GABA-B/metabolism ; Smell/drug effects/physiology ; gamma-Aminobutyric Acid/metabolism/pharmacology
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  • 9
    Publication Date: 2008-03-21
    Description: Equal amounts of matter and antimatter are predicted to have been produced in the Big Bang, but our observable Universe is clearly matter-dominated. One of the prerequisites for understanding this elimination of antimatter is the nonconservation of charge-parity (CP) symmetry. So far, two types of CP violation have been observed in the neutral K meson (K(0)) and B meson (B(0)) systems: CP violation involving the mixing between K(0) and its antiparticle (and likewise for B(0) and ), and direct CP violation in the decay of each meson. The observed effects for both types of CP violation are substantially larger for the B(0) meson system. However, they are still consistent with the standard model of particle physics, which has a unique source of CP violation that is known to be too small to account for the matter-dominated Universe. Here we report that the direct CP violation in charged B(+/-)--〉K(+/-)pi(0) decay is different from that in the neutral B(0) counterpart. The direct CP-violating decay rate asymmetry, (that is, the difference between the number of observed B(-)--〉K(-)pi(0) event versus B(+)--〉K(+) pi(0) events, normalized to the sum of these events) is measured to be about +7%, with an uncertainty that is reduced by a factor of 1.7 from a previous measurement. However, the asymmetry for versus B(0)--〉K(+)pi(-) is at the -10% level. Although it is susceptible to strong interaction effects that need further clarification, this large deviation in direct CP violation between charged and neutral B meson decays could be an indication of new sources of CP violation-which would help to explain the dominance of matter in the Universe.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Belle Collaboration -- Lin, S-W -- Unno, Y -- Hou, W-S -- Chang, P -- Adachi, I -- Aihara, H -- Akai, K -- Arinstein, K -- Aulchenko, V -- Aushev, T -- Aziz, T -- Bakich, A M -- Balagura, V -- Barberio, E -- Bay, A -- Bedny, I -- Bitenc, U -- Bondar, A -- Bozek, A -- Bracko, M -- Browder, T E -- Chang, M-C -- Chao, Y -- Chen, A -- Chen, K-F -- Chen, W T -- Cheon, B G -- Chiang, C-C -- Chistov, R -- Cho, I-S -- Choi, S-K -- Choi, Y -- Choi, Y K -- Cole, S -- Dalseno, J -- Danilov, M -- Dash, M -- Drutskoy, A -- Eidelman, S -- Epifanov, D -- Fratina, S -- Fujikawa, M -- Furukawa, K -- Gabyshev, N -- Goldenzweig, P -- Golob, B -- Ha, H -- Haba, J -- Hara, T -- Hayasaka, K -- Hayashii, H -- Hazumi, M -- Heffernan, D -- Hokuue, T -- Hoshi, Y -- Hsiung, Y B -- Hyun, H J -- Iijima, T -- Ikado, K -- Inami, K -- Ishikawa, A -- Ishino, H -- Itoh, R -- Iwabuchi, M -- Iwasaki, M -- Iwasaki, Y -- Kah, D H -- Kaji, H -- Kataoka, S U -- Kawai, H -- Kawasaki, T -- Kibayashi, A -- Kichimi, H -- Kikutani, E -- Kim, H J -- Kim, S K -- Kim, Y J -- Kinoshita, K -- Korpar, S -- Kozakai, Y -- Krizan, P -- Krokovny, P -- Kumar, R -- Kuo, C C -- Kuzmin, A -- Kwon, Y-J -- Lee, M J -- Lee, S E -- Lesiak, T -- Li, J -- Liu, Y -- Liventsev, D -- Mandl, F -- Marlow, D -- McOnie, S -- Medvedeva, T -- Mimashi, T -- Mitaroff, W -- Miyabayashi, K -- Miyake, H -- Miyazaki, Y -- Mizuk, R -- Mori, T -- Nakamura, T T -- Nakano, E -- Nakao, M -- Nakazawa, H -- Nishida, S -- Nitoh, O -- Noguchi, S -- Nozaki, T -- Ogawa, S -- Ogawa, Y -- Ohshima, T -- Okuno, S -- Olsen, S L -- Ozaki, H -- Pakhlova, G -- Park, C W -- Park, H -- Peak, L S -- Pestotnik, R -- Peters, M -- Piilonen, L E -- Poluektov, A -- Sahoo, H -- Sakai, Y -- Schneider, O -- Schumann, J -- Schwartz, A J -- Seidl, R -- Senyo, K -- Sevior, M E -- Shapkin, M -- Shen, C P -- Shibuya, H -- Shidara, T -- Shinomiya, S -- Shiu, J-G -- Shwartz, B -- Singh, J B -- Sokolov, A -- Somov, A -- Stanic, S -- Staric, M -- Sumisawa, K -- Sumiyoshi, T -- Suzuki, S -- Tajima, O -- Takasaki, F -- Tamura, N -- Tanaka, M -- Tawada, M -- Taylor, G N -- Teramoto, Y -- Tikhomirov, I -- Trabelsi, K -- Uehara, S -- Ueno, K -- Uglov, T -- Uno, S -- Urquijo, P -- Ushiroda, Y -- Usov, Y -- Varner, G -- Varvell, K E -- Vervink, K -- Villa, S -- Wang, C C -- Wang, C H -- Wang, M-Z -- Watanabe, Y -- Wedd, R -- Wicht, J -- Won, E -- Yabsley, B D -- Yamaguchi, A -- Yamashita, Y -- Yamauchi, M -- Yoshida, M -- Yuan, C Z -- Yusa, Y -- Zhang, C C -- Zhang, Z P -- Zhilich, V -- Zhulanov, V -- Zupanc, A -- England -- Nature. 2008 Mar 20;452(7185):332-5. doi: 10.1038/nature06827.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, National Taiwan University, Taipei, 106, Taiwan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18354478" target="_blank"〉PubMed〈/a〉
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  • 10
    Publication Date: 2010-01-30
    Description: Heat shock protein 70 (Hsp70) is an evolutionarily highly conserved molecular chaperone that promotes the survival of stressed cells by inhibiting lysosomal membrane permeabilization, a hallmark of stress-induced cell death. Clues to its molecular mechanism of action may lay in the recently reported stress- and cancer-associated translocation of a small portion of Hsp70 to the lysosomal compartment. Here we show that Hsp70 stabilizes lysosomes by binding to an endolysosomal anionic phospholipid bis(monoacylglycero)phosphate (BMP), an essential co-factor for lysosomal sphingomyelin metabolism. In acidic environments Hsp70 binds with high affinity and specificity to BMP, thereby facilitating the BMP binding and activity of acid sphingomyelinase (ASM). The inhibition of the Hsp70-BMP interaction by BMP antibodies or a point mutation in Hsp70 (Trp90Phe), as well as the pharmacological and genetic inhibition of ASM, effectively revert the Hsp70-mediated stabilization of lysosomes. Notably, the reduced ASM activity in cells from patients with Niemann-Pick disease (NPD) A and B-severe lysosomal storage disorders caused by mutations in the sphingomyelin phosphodiesterase 1 gene (SMPD1) encoding for ASM-is also associated with a marked decrease in lysosomal stability, and this phenotype can be effectively corrected by treatment with recombinant Hsp70. Taken together, these data open exciting possibilities for the development of new treatments for lysosomal storage disorders and cancer with compounds that enter the lysosomal lumen by the endocytic delivery pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kirkegaard, Thomas -- Roth, Anke G -- Petersen, Nikolaj H T -- Mahalka, Ajay K -- Olsen, Ole Dines -- Moilanen, Irina -- Zylicz, Alicja -- Knudsen, Jens -- Sandhoff, Konrad -- Arenz, Christoph -- Kinnunen, Paavo K J -- Nylandsted, Jesper -- Jaattela, Marja -- England -- Nature. 2010 Jan 28;463(7280):549-53. doi: 10.1038/nature08710.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Apoptosis Department and Centre for Genotoxic Stress Research, Institute of Cancer Biology, Danish Cancer Society, DK-2100 Copenhagen, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20111001" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line, Tumor ; Cells, Cultured ; HSP70 Heat-Shock Proteins/*metabolism ; Humans ; Hydrogen-Ion Concentration ; Intracellular Membranes/metabolism ; Lysophospholipids/metabolism ; Lysosomes/*metabolism/*pathology ; Monoglycerides/metabolism ; Niemann-Pick Diseases/*metabolism/*pathology ; Sphingomyelin Phosphodiesterase/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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