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  • 1
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    Atomic structure of the cubic core of the pyruvate dehydrogenase multienzyme complex (1992)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1992-03-20
    Description: The highly symmetric pyruvate dehydrogenase multienzyme complexes have molecular masses ranging from 5 to 10 million daltons. They consist of numerous copies of three different enzymes: pyruvate dehydrogenase, dihydrolipoyl transacetylase, and lipoamide dehydrogenase. The three-dimensional crystal structure of the catalytic domain of Azotobacter vinelandii dihydrolipoyl transacetylase has been determined at 2.6 angstrom (A) resolution. Eight trimers assemble as a hollow truncated cube with an edge of 125 A, forming the core of the multienzyme complex. Coenzyme A must enter the 29 A long active site channel from the inside of the cube, and lipoamide must enter from the outside. The trimer of the catalytic domain of dihydrolipoyl transacetylase has a topology identical to chloramphenicol acetyl transferase. The atomic structure of the 24-subunit cube core provides a framework for understanding all pyruvate dehydrogenase and related multienzyme complexes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mattevi, A -- Obmolova, G -- Schulze, E -- Kalk, K H -- Westphal, A H -- de Kok, A -- Hol, W G -- New York, N.Y. -- Science. 1992 Mar 20;255(5051):1544-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Groningen, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1549782" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Azotobacter vinelandii/enzymology ; Chloramphenicol O-Acetyltransferase/genetics ; Humans ; Models, Molecular ; Molecular Sequence Data ; Molecular Structure ; Pyruvate Dehydrogenase Complex/*chemistry/genetics ; Sequence Homology, Nucleic Acid
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    Inclusion of thermal motion in crystallographic structures by restrained molecular dynamics (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-09-07
    Description: A protein crystal structure is usually described by one single structure, which largely omits the dynamical behavior of the molecule. A molecular dynamics method with a time-averaged crystallographic restraint was used to overcome this limitation. This method yields an ensemble of structures in which all possible thermal motions are allowed, that is, in additional to isotropic distributions, anisotropic and anharmonic positional distributions occur as well. In the case of bovine pancreatic phospholipase A2, this description markedly improves agreement with the observed x-ray diffraction data compared to the results of the classical one-model structure description. Time-averaged crystallographically restrained molecular dynamics reveals large mobilities in the loops involved in lipid bilayer association.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gros, P -- van Gunsteren, W F -- Hol, W G -- New York, N.Y. -- Science. 1990 Sep 7;249(4973):1149-52.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉BIOSON Research Institute, University of Groningen, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2396108" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cattle ; Crystallography ; Hot Temperature ; Models, Molecular ; Motion ; *Phospholipases ; *Phospholipases A ; Phospholipases A2 ; Protein Conformation ; X-Ray Diffraction
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    EGF receptor and erbB-2 tyrosine kinase domains confer cell specificity for mitogenic signaling (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-04-06
    Description: The epidermal growth factor (EGF) receptor (EGFR) can efficiently couple with mitogenic signaling pathways when it is transfected into interleukin-3 (IL-3)-dependent 32D hematopoietic cells. When expression vectors for erbB-2, which is structurally related to EGFR, or its truncated counterpart, delta NerbB-2, were introduced into 32D cells, neither was capable of inducing proliferation. This was despite overexpression and constitutive tyrosine kinase activity of their products at levels associated with potent transformation of fibroblast target cells. Thus, EGFR and erbB-2 couple with distinct mitogenic signaling pathways. The region responsible for the specificity of intracellular signal transduction was localized to a 270-amino acid stretch encompassing their respective tyrosine kinase domains. Thus, tissue- or cell-specific regulation of growth factor receptor signaling can occur at a point after the initial interaction of growth factor with receptor. Such specificity in signal transduction may account for the selection of certain oncogenes in some malignancies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Di Fiore, P P -- Segatto, O -- Taylor, W G -- Aaronson, S A -- Pierce, J H -- New York, N.Y. -- Science. 1990 Apr 6;248(4951):79-83.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2181668" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Division ; Cell Line ; DNA/genetics ; DNA, Recombinant ; Fibroblasts/cytology/metabolism ; Gene Expression ; Genetic Vectors ; Hematopoietic Stem Cells/cytology/metabolism ; Immunoblotting ; Mice ; *Mitogens ; Molecular Sequence Data ; Protein-Tyrosine Kinases/genetics/*physiology ; Proto-Oncogene Proteins/genetics/*physiology ; Receptor, Epidermal Growth Factor/genetics/*physiology ; Sequence Homology, Nucleic Acid ; Signal Transduction ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    Visualization of quantal synaptic transmission by dendritic calcium imaging (1994)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1994-01-28
    Description: As changes in synaptic strength are thought to be critical for learning and memory, it would be useful to monitor the activity of individual identified synapses on mammalian central neurons. Calcium imaging of cortical neurons grown in primary culture was used to visualize the activation of individual postsynaptic elements by miniature excitatory synaptic currents elicited by spontaneous quantal release. This approach revealed that the probability of spontaneous activity differed among synapses on the same dendrite. Furthermore, synapses that undergo changes in activity induced by glutamate or phorbol ester treatment were identified.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murphy, T H -- Baraban, J M -- Wier, W G -- Blatter, L A -- New York, N.Y. -- Science. 1994 Jan 28;263(5146):529-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7904774" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism ; Cells, Cultured ; Cerebral Cortex ; Dendrites/*metabolism ; Glutamates/pharmacology ; Glutamic Acid ; Kinetics ; Microelectrodes ; Neuronal Plasticity ; Neurons/*physiology ; Phorbol Esters/pharmacology ; Rats ; Receptors, N-Methyl-D-Aspartate/physiology ; Synapses/*physiology ; *Synaptic Transmission ; Tetrodotoxin/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    CD26 antigen and HIV fusion? (1994)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1994-05-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Broder, C C -- Nussbaum, O -- Gutheil, W G -- Bachovchin, W W -- Berger, E A -- New York, N.Y. -- Science. 1994 May 20;264(5162):1156-9; author reply 1162-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7909959" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD4/*physiology ; Antigens, Differentiation, T-Lymphocyte/*physiology ; Base Sequence ; *Cell Fusion ; Cell Line ; Dipeptidyl Peptidase 4 ; Gene Products, env/*physiology ; Giant Cells/physiology ; HIV-1/*physiology ; Humans ; Hybrid Cells ; Molecular Sequence Data
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    Regulation of the Ets-related transcription factor Elf-1 by binding to the retinoblastoma protein (1993)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1993-05-28
    Description: The retinoblastoma gene product (Rb) is a nuclear phosphoprotein that regulates cell cycle progression. Elf-1 is a lymphoid-specific Ets transcription factor that regulates inducible gene expression during T cell activation. In this report, it is demonstrated that Elf-1 contains a sequence motif that is highly related to the Rb binding sites of several viral oncoproteins and binds to the pocket region of Rb both in vitro and in vivo. Elf-1 binds exclusively to the underphosphorylated form of Rb and fails to bind to Rb mutants derived from patients with retinoblastoma. Co-immunoprecipitation experiments demonstrated an association between Elf-1 and Rb in resting normal human T cells. After T cell activation, the phosphorylation of Rb results in the release of Elf-1, which is correlated temporally with the activation of Elf-1-mediated transcription. Overexpression of a phosphorylation-defective form of Rb inhibited Elf-1-dependent transcription during T cell activation. These results demonstrate that Rb interacts specifically with a lineage-restricted Ets transcription factor. This regulated interaction may be important for the coordination of lineage-specific effector functions such as lymphokine production with cell cycle progression in activated T cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, C Y -- Petryniak, B -- Thompson, C B -- Kaelin, W G -- Leiden, J M -- R01 AI29673-01/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1993 May 28;260(5112):1330-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Chicago, IL 60637.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8493578" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; Cell Cycle ; Cell Line ; DNA-Binding Proteins/chemistry/*metabolism ; Eye Neoplasms/genetics ; Humans ; Lymphocyte Activation ; Molecular Sequence Data ; Mutation ; Oligodeoxyribonucleotides ; Phosphorylation ; Recombinant Fusion Proteins/metabolism ; Retinoblastoma/genetics ; Retinoblastoma Protein/*metabolism ; T-Lymphocytes/immunology/*metabolism ; Transcription Factors/chemistry/*metabolism ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    A skin-inspired organic digital mechanoreceptor (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-10-17
    Description: Human skin relies on cutaneous receptors that output digital signals for tactile sensing in which the intensity of stimulation is converted to a series of voltage pulses. We present a power-efficient skin-inspired mechanoreceptor with a flexible organic transistor circuit that transduces pressure into digital frequency signals directly. The output frequency ranges between 0 and 200 hertz, with a sublinear response to increasing force stimuli that mimics slow-adapting skin mechanoreceptors. The output of the sensors was further used to stimulate optogenetically engineered mouse somatosensory neurons of mouse cortex in vitro, achieving stimulated pulses in accordance with pressure levels. This work represents a step toward the design and use of large-area organic electronic skins with neural-integrated touch feedback for replacement limbs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tee, Benjamin C-K -- Chortos, Alex -- Berndt, Andre -- Nguyen, Amanda Kim -- Tom, Ariane -- McGuire, Allister -- Lin, Ziliang Carter -- Tien, Kevin -- Bae, Won-Gyu -- Wang, Huiliang -- Mei, Ping -- Chou, Ho-Hsiu -- Cui, Bianxiao -- Deisseroth, Karl -- Ng, Tse Nga -- Bao, Zhenan -- New York, N.Y. -- Science. 2015 Oct 16;350(6258):313-6. doi: 10.1126/science.aaa9306.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Electrical Engineering, Stanford University, Stanford, CA, USA. ; Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA. ; Department of Bioengineering, Stanford University, Stanford, CA, USA. ; Department of Chemistry, Stanford University, Stanford, CA, USA. ; Department of Chemical Engineering, Stanford University, Stanford, CA, USA. ; Xerox Palo Alto Research Center, Palo Alto, CA, USA. ; Department of Chemical Engineering, Stanford University, Stanford, CA, USA. zbao@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472906" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cerebral Cortex/cytology/physiology ; Hand/anatomy & histology/innervation/physiology ; Humans ; In Vitro Techniques ; *Mechanoreceptors ; Mice ; *Neural Prostheses ; Optogenetics ; Pressure ; Skin/*innervation ; *Touch ; Transcutaneous Electric Nerve Stimulation/*methods ; Transistors, Electronic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    Algal toxin impairs sea lion memory and hippocampal connectivity, with implications for strandings (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-12-17
    Description: Domoic acid (DA) is a naturally occurring neurotoxin known to harm marine animals. DA-producing algal blooms are increasing in size and frequency. Although chronic exposure is known to produce brain lesions, the influence of DA toxicosis on behavior in wild animals is unknown. We showed, in a large sample of wild sea lions, that spatial memory deficits are predicted by the extent of right dorsal hippocampal lesions related to natural exposure to DA and that exposure also disrupts hippocampal-thalamic brain networks. Because sea lions are dynamic foragers that rely on flexible navigation, impaired spatial memory may affect survival in the wild.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cook, Peter F -- Reichmuth, Colleen -- Rouse, Andrew A -- Libby, Laura A -- Dennison, Sophie E -- Carmichael, Owen T -- Kruse-Elliott, Kris T -- Bloom, Josh -- Singh, Baljeet -- Fravel, Vanessa A -- Barbosa, Lorraine -- Stuppino, Jim J -- Van Bonn, William G -- Gulland, Frances M D -- Ranganath, Charan -- New York, N.Y. -- Science. 2015 Dec 18;350(6267):1545-7. doi: 10.1126/science.aac5675. Epub 2015 Dec 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neuropolicy, Emory University, Atlanta, GA 30322, USA. Pinniped Cognition and Sensory Systems Laboratory, Institute of Marine Sciences, University of California-Santa Cruz, Santa Cruz, CA 95060, USA. pfcook@emory.edu. ; Pinniped Cognition and Sensory Systems Laboratory, Institute of Marine Sciences, University of California-Santa Cruz, Santa Cruz, CA 95060, USA. ; Dynamic Memory Lab, Center for Neuroscience, University of California-Davis, Davis, CA 95618, USA. ; AnimalScan Advanced Veterinary Imaging, Redwood City, CA 94063, USA. ; Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA. ; The Marine Mammal Center, Sausalito, CA 94965, USA. ; Shedd Aquarium, Chicago, IL 60605, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26668068" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Eutrophication ; Hippocampus/*drug effects/physiology ; Kainic Acid/*analogs & derivatives/metabolism/toxicity ; Marine Toxins/*toxicity ; Neurotoxins/metabolism/*toxicity ; Sea Lions/*physiology ; Spatial Memory/*drug effects ; Thalamus/drug effects/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
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    The calcium sensor synaptotagmin 7 is required for synaptic facilitation (2016)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2016-01-08
    Description: It has been known for more than 70 years that synaptic strength is dynamically regulated in a use-dependent manner. At synapses with a low initial release probability, closely spaced presynaptic action potentials can result in facilitation, a short-term form of enhancement in which each subsequent action potential evokes greater neurotransmitter release. Facilitation can enhance neurotransmitter release considerably and can profoundly influence information transfer across synapses, but the underlying mechanism remains a mystery. One proposed mechanism is that a specialized calcium sensor for facilitation transiently increases the probability of release, and this sensor is distinct from the fast sensors that mediate rapid neurotransmitter release. Yet such a sensor has never been identified, and its very existence has been disputed. Here we show that synaptotagmin 7 (Syt7) is a calcium sensor that is required for facilitation at several central synapses. In Syt7-knockout mice, facilitation is eliminated even though the initial probability of release and the presynaptic residual calcium signals are unaltered. Expression of wild-type Syt7 in presynaptic neurons restored facilitation, whereas expression of a mutated Syt7 with a calcium-insensitive C2A domain did not. By revealing the role of Syt7 in synaptic facilitation, these results resolve a longstanding debate about a widespread form of short-term plasticity, and will enable future studies that may lead to a deeper understanding of the functional importance of facilitation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729191/" 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/PMC4729191/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jackman, Skyler L -- Turecek, Josef -- Belinsky, Justine E -- Regehr, Wade G -- NS032405/NS/NINDS NIH HHS/ -- P30 NS072030/NS/NINDS NIH HHS/ -- R01 NS032405/NS/NINDS NIH HHS/ -- England -- Nature. 2016 Jan 7;529(7584):88-91. doi: 10.1038/nature16507.〈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/26738595" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism ; Calcium Signaling ; Female ; Male ; Mice ; Mice, Knockout ; Neuronal Plasticity ; Neurons/metabolism/secretion ; Neurotransmitter Agents/*secretion ; Presynaptic Terminals/metabolism ; Synapses/*metabolism/secretion ; *Synaptic Transmission ; Synaptotagmins/deficiency/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 10
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    Anti-HIV and anti-anti-MHC antibodies in alloimmune and autoimmune mice (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-09-06
    Description: Alloimmune mice (mice that have been exposed to cells from another murine strain) were shown to make antibodies against gp120 and p24 of human immunodeficiency virus (HIV), and mice of the autoimmune strains MRL-lpr/lpr and MRL-(+)/+ made antibodies against gp120. This is surprising because the mice were not exposed to HIV. Furthermore, anti-anti-MHC antibodies (molecules that have shapes similar to those of major histocompatibility complex molecules) were detected in both alloimmune sera and MRL mice. These results are discussed in the context of a possible role for allogeneic stimuli in the pathogenesis of acquired immunodeficiency syndrome, as suggested by an idiotypic network model.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kion, T A -- Hoffmann, G W -- New York, N.Y. -- Science. 1991 Sep 6;253(5024):1138-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of British Columbia, Vancouver, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1909456" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal ; *Antibody Formation ; Autoimmune Diseases/genetics/*immunology/microbiology ; Enzyme-Linked Immunosorbent Assay ; Gene Products, gag/*immunology ; HIV Antibodies/*biosynthesis ; HIV Antigens/*immunology ; HIV Core Protein p24 ; HIV Envelope Protein gp120/*immunology ; Histocompatibility Antigens Class II/*immunology ; Isoantibodies/*biosynthesis ; *Major Histocompatibility Complex ; Mice ; Mice, Inbred BALB C ; Mice, Inbred CBA ; Mice, Mutant Strains ; T-Lymphocytes/immunology ; Viral Core Proteins/*immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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