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  • 1
    Publication Date: 2014-08-15
    Description: Neurotransmitter-gated ion channels of the Cys-loop receptor family mediate fast neurotransmission throughout the nervous system. The molecular processes of neurotransmitter binding, subsequent opening of the ion channel and ion permeation remain poorly understood. Here we present the X-ray structure of a mammalian Cys-loop receptor, the mouse serotonin 5-HT3 receptor, at 3.5 A resolution. The structure of the proteolysed receptor, made up of two fragments and comprising part of the intracellular domain, was determined in complex with stabilizing nanobodies. The extracellular domain reveals the detailed anatomy of the neurotransmitter binding site capped by a nanobody. The membrane domain delimits an aqueous pore with a 4.6 A constriction. In the intracellular domain, a bundle of five intracellular helices creates a closed vestibule where lateral portals are obstructed by loops. This 5-HT3 receptor structure, revealing part of the intracellular domain, expands the structural basis for understanding the operating mechanism of mammalian Cys-loop receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hassaine, Gherici -- Deluz, Cedric -- Grasso, Luigino -- Wyss, Romain -- Tol, Menno B -- Hovius, Ruud -- Graff, Alexandra -- Stahlberg, Henning -- Tomizaki, Takashi -- Desmyter, Aline -- Moreau, Christophe -- Li, Xiao-Dan -- Poitevin, Frederic -- Vogel, Horst -- Nury, Hugues -- England -- Nature. 2014 Aug 21;512(7514):276-81. doi: 10.1038/nature13552. Epub 2014 Aug 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland [2] [3] Theranyx, 163 Avenue de Luminy, 13288 Marseille, France. ; 1] Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland [2]. ; Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland. ; Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, CH-4058 Basel, Switzerland. ; Swiss Light Source, Paul Scherrer Institute, CH-5234 Villigen, Switzerland. ; Architecture et Fonction des Macromolecules Biologiques, CNRS UMR 7257 and Universite Aix-Marseille, F-13288 Marseille, France. ; 1] Universite Grenoble Alpes, IBS, F-38000 Grenoble, France [2] CNRS, IBS, F-38000 Grenoble, France [3] CEA, DSV, IBS, F-38000 Grenoble, France. ; Laboratory of Biomolecular Research, Paul Scherrer Institute, CH-5232 Villigen, Switzerland. ; Unite de Dynamique Structurale des Macromolecules, Institut Pasteur, CNRS UMR3528, F-75015 Paris, France. ; 1] Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland [2] Universite Grenoble Alpes, IBS, F-38000 Grenoble, France [3] CNRS, IBS, F-38000 Grenoble, France [4] CEA, DSV, IBS, F-38000 Grenoble, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119048" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Crystallography, X-Ray ; Mice ; Models, Molecular ; Molecular Sequence Data ; Neurotransmitter Agents/metabolism ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Protein Subunits/chemistry/metabolism ; Receptors, Serotonin, 5-HT3/*chemistry/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2012-07-18
    Description: The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved. One contentious issue is whether the settlement occurred by means of a single migration or multiple streams of migration from Siberia. The pattern of dispersals within the Americas is also poorly understood. To address these questions at a higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. Here we show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call 'First American'. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615710/" 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/PMC3615710/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reich, David -- Patterson, Nick -- Campbell, Desmond -- Tandon, Arti -- Mazieres, Stephane -- Ray, Nicolas -- Parra, Maria V -- Rojas, Winston -- Duque, Constanza -- Mesa, Natalia -- Garcia, Luis F -- Triana, Omar -- Blair, Silvia -- Maestre, Amanda -- Dib, Juan C -- Bravi, Claudio M -- Bailliet, Graciela -- Corach, Daniel -- Hunemeier, Tabita -- Bortolini, Maria Catira -- Salzano, Francisco M -- Petzl-Erler, Maria Luiza -- Acuna-Alonzo, Victor -- Aguilar-Salinas, Carlos -- Canizales-Quinteros, Samuel -- Tusie-Luna, Teresa -- Riba, Laura -- Rodriguez-Cruz, Maricela -- Lopez-Alarcon, Mardia -- Coral-Vazquez, Ramon -- Canto-Cetina, Thelma -- Silva-Zolezzi, Irma -- Fernandez-Lopez, Juan Carlos -- Contreras, Alejandra V -- Jimenez-Sanchez, Gerardo -- Gomez-Vazquez, Maria Jose -- Molina, Julio -- Carracedo, Angel -- Salas, Antonio -- Gallo, Carla -- Poletti, Giovanni -- Witonsky, David B -- Alkorta-Aranburu, Gorka -- Sukernik, Rem I -- Osipova, Ludmila -- Fedorova, Sardana A -- Vasquez, Rene -- Villena, Mercedes -- Moreau, Claudia -- Barrantes, Ramiro -- Pauls, David -- Excoffier, Laurent -- Bedoya, Gabriel -- Rothhammer, Francisco -- Dugoujon, Jean-Michel -- Larrouy, Georges -- Klitz, William -- Labuda, Damian -- Kidd, Judith -- Kidd, Kenneth -- Di Rienzo, Anna -- Freimer, Nelson B -- Price, Alkes L -- Ruiz-Linares, Andres -- BB/1021213/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- GM057672/GM/NIGMS NIH HHS/ -- GM079558/GM/NIGMS NIH HHS/ -- GM079558-S1/GM/NIGMS NIH HHS/ -- HG006399/HG/NHGRI NIH HHS/ -- MH075007/MH/NIMH NIH HHS/ -- NS037484/NS/NINDS NIH HHS/ -- NS043538/NS/NINDS NIH HHS/ -- R01 GM079558/GM/NIGMS NIH HHS/ -- R01 GM100233/GM/NIGMS NIH HHS/ -- R01 HG006399/HG/NHGRI NIH HHS/ -- R21 DK073818/DK/NIDDK NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2012 Aug 16;488(7411):370-4. doi: 10.1038/nature11258.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. reich@genetics.med.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22801491" target="_blank"〉PubMed〈/a〉
    Keywords: Americas ; Asia ; Cluster Analysis ; Emigration and Immigration/*history/statistics & numerical data ; Gene Flow ; Genetics, Population ; History, Ancient ; Humans ; Indians, North American/*genetics/*history ; Models, Genetic ; *Phylogeny ; Polymorphism, Single Nucleotide/genetics ; Siberia
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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