ALBERT

Description: The identification of proximate amino acids by chemical cross-linking and mass spectrometry (XL-MS) facilitates the structural analysis of homogeneous protein complexes. We gained distance restraints on a modular interaction network of protein complexes affinity-purified from human cells by applying an adapted XL-MS protocol. Systematic analysis of human protein phosphatase 2A (PP2A) complexes identified 176 interprotein and 570 intraprotein cross-links that link specific trimeric PP2A complexes to a multitude of adaptor proteins that control their cellular functions. Spatial restraints guided molecular modeling of the binding interface between immunoglobulin binding protein 1 (IGBP1) and PP2A and revealed the topology of TCP1 ring complex (TRiC) chaperonin interacting with the PP2A regulatory subunit 2ABG. This study establishes XL-MS as an integral part of hybrid structural biology approaches for the analysis of endogenous protein complexes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herzog, Franz -- Kahraman, Abdullah -- Boehringer, Daniel -- Mak, Raymond -- Bracher, Andreas -- Walzthoeni, Thomas -- Leitner, Alexander -- Beck, Martin -- Hartl, Franz-Ulrich -- Ban, Nenad -- Malmstrom, Lars -- Aebersold, Ruedi -- New York, N.Y. -- Science. 2012 Sep 14;337(6100):1348-52. doi: 10.1126/science.1221483.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Institute of Molecular Systems Biology, Eidgenossische Technische Hochschule Zurich, Wolfgang-Pauli Strasse 16, 8093 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22984071" target="_blank"〉PubMed〈/a〉

Description: Genome-wide association studies (GWAS) have identified common variants of modest-effect size at hundreds of loci for common autoimmune diseases; however, a substantial fraction of heritability remains unexplained, to which rare variants may contribute. To discover rare variants and test them for association with a phenotype, most studies re-sequence a small initial sample size and then genotype the discovered variants in a larger sample set. This approach fails to analyse a large fraction of the rare variants present in the entire sample set. Here we perform simultaneous amplicon-sequencing-based variant discovery and genotyping for coding exons of 25 GWAS risk genes in 41,911 UK residents of white European origin, comprising 24,892 subjects with six autoimmune disease phenotypes and 17,019 controls, and show that rare coding-region variants at known loci have a negligible role in common autoimmune disease susceptibility. These results do not support the rare-variant synthetic genome-wide-association hypothesis (in which unobserved rare causal variants lead to association detected at common tag variants). Many known autoimmune disease risk loci contain multiple, independently associated, common and low-frequency variants, and so genes at these loci are a priori stronger candidates for harbouring rare coding-region variants than other genes. Our data indicate that the missing heritability for common autoimmune diseases may not be attributable to the rare coding-region variant portion of the allelic spectrum, but perhaps, as others have proposed, may be a result of many common-variant loci of weak effect.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736321/" 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/PMC3736321/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hunt, Karen A -- Mistry, Vanisha -- Bockett, Nicholas A -- Ahmad, Tariq -- Ban, Maria -- Barker, Jonathan N -- Barrett, Jeffrey C -- Blackburn, Hannah -- Brand, Oliver -- Burren, Oliver -- Capon, Francesca -- Compston, Alastair -- Gough, Stephen C L -- Jostins, Luke -- Kong, Yong -- Lee, James C -- Lek, Monkol -- MacArthur, Daniel G -- Mansfield, John C -- Mathew, Christopher G -- Mein, Charles A -- Mirza, Muddassar -- Nutland, Sarah -- Onengut-Gumuscu, Suna -- Papouli, Efterpi -- Parkes, Miles -- Rich, Stephen S -- Sawcer, Steven -- Satsangi, Jack -- Simmonds, Matthew J -- Trembath, Richard C -- Walker, Neil M -- Wozniak, Eva -- Todd, John A -- Simpson, Michael A -- Plagnol, Vincent -- van Heel, David A -- 068181/Wellcome Trust/United Kingdom -- 068545/Z/02/Wellcome Trust/United Kingdom -- 076113/C/04/Z/Wellcome Trust/United Kingdom -- 091157/Wellcome Trust/United Kingdom -- 100140/Wellcome Trust/United Kingdom -- CZB/4/540/Chief Scientist Office/United Kingdom -- ETM/137/Chief Scientist Office/United Kingdom -- ETM/75/Chief Scientist Office/United Kingdom -- G0000934/Medical Research Council/United Kingdom -- G0600329/Medical Research Council/United Kingdom -- G0601387/Medical Research Council/United Kingdom -- G0800759/Medical Research Council/United Kingdom -- G1001158/Medical Research Council/United Kingdom -- G1001158(95979)/Medical Research Council/United Kingdom -- JDRF 4-2001-1008/Wellcome Trust/United Kingdom -- WT061858/Wellcome Trust/United Kingdom -- England -- Nature. 2013 Jun 13;498(7453):232-5. doi: 10.1038/nature12170. Epub 2013 May 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23698362" target="_blank"〉PubMed〈/a〉

Description: Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182531/" 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/PMC3182531/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉International Multiple Sclerosis Genetics Consortium -- Wellcome Trust Case Control Consortium 2 -- Sawcer, Stephen -- Hellenthal, Garrett -- Pirinen, Matti -- Spencer, Chris C A -- Patsopoulos, Nikolaos A -- Moutsianas, Loukas -- Dilthey, Alexander -- Su, Zhan -- Freeman, Colin -- Hunt, Sarah E -- Edkins, Sarah -- Gray, Emma -- Booth, David R -- Potter, Simon C -- Goris, An -- Band, Gavin -- Oturai, Annette Bang -- Strange, Amy -- Saarela, Janna -- Bellenguez, Celine -- Fontaine, Bertrand -- Gillman, Matthew -- Hemmer, Bernhard -- Gwilliam, Rhian -- Zipp, Frauke -- Jayakumar, Alagurevathi -- Martin, Roland -- Leslie, Stephen -- Hawkins, Stanley -- Giannoulatou, Eleni -- D'alfonso, Sandra -- Blackburn, Hannah -- Martinelli Boneschi, Filippo -- Liddle, Jennifer -- Harbo, Hanne F -- Perez, Marc L -- Spurkland, Anne -- Waller, Matthew J -- Mycko, Marcin P -- Ricketts, Michelle -- Comabella, Manuel -- Hammond, Naomi -- Kockum, Ingrid -- McCann, Owen T -- Ban, Maria -- Whittaker, Pamela -- Kemppinen, Anu -- Weston, Paul -- Hawkins, Clive -- Widaa, Sara -- Zajicek, John -- Dronov, Serge -- Robertson, Neil -- Bumpstead, Suzannah J -- Barcellos, Lisa F -- Ravindrarajah, Rathi -- Abraham, Roby -- Alfredsson, Lars -- Ardlie, Kristin -- Aubin, Cristin -- Baker, Amie -- Baker, Katharine -- Baranzini, Sergio E -- Bergamaschi, Laura -- Bergamaschi, Roberto -- Bernstein, Allan -- Berthele, Achim -- Boggild, Mike -- Bradfield, Jonathan P -- Brassat, David -- Broadley, Simon A -- Buck, Dorothea -- Butzkueven, Helmut -- Capra, Ruggero -- Carroll, William M -- Cavalla, Paola -- Celius, Elisabeth G -- Cepok, Sabine -- Chiavacci, Rosetta -- Clerget-Darpoux, Francoise -- Clysters, Katleen -- Comi, Giancarlo -- Cossburn, Mark -- Cournu-Rebeix, Isabelle -- Cox, Mathew B -- Cozen, Wendy -- Cree, Bruce A C -- Cross, Anne H -- Cusi, Daniele -- Daly, Mark J -- Davis, Emma -- de Bakker, Paul I W -- Debouverie, Marc -- D'hooghe, Marie Beatrice -- Dixon, Katherine -- Dobosi, Rita -- Dubois, Benedicte -- Ellinghaus, David -- Elovaara, Irina -- Esposito, Federica -- Fontenille, Claire -- Foote, Simon -- Franke, Andre -- Galimberti, Daniela -- Ghezzi, Angelo -- Glessner, Joseph -- Gomez, Refujia -- Gout, Olivier -- Graham, Colin -- Grant, Struan F A -- Guerini, Franca Rosa -- Hakonarson, Hakon -- Hall, Per -- Hamsten, Anders -- Hartung, Hans-Peter -- Heard, Rob N -- Heath, Simon -- Hobart, Jeremy -- Hoshi, Muna -- Infante-Duarte, Carmen -- Ingram, Gillian -- Ingram, Wendy -- Islam, Talat -- Jagodic, Maja -- Kabesch, Michael -- Kermode, Allan G -- Kilpatrick, Trevor J -- Kim, Cecilia -- Klopp, Norman -- Koivisto, Keijo -- Larsson, Malin -- Lathrop, Mark -- Lechner-Scott, Jeannette S -- Leone, Maurizio A -- Leppa, Virpi -- Liljedahl, Ulrika -- Bomfim, Izaura Lima -- Lincoln, Robin R -- Link, Jenny -- Liu, Jianjun -- Lorentzen, Aslaug R -- Lupoli, Sara -- Macciardi, Fabio -- Mack, Thomas -- Marriott, Mark -- Martinelli, Vittorio -- Mason, Deborah -- McCauley, Jacob L -- Mentch, Frank -- Mero, Inger-Lise -- Mihalova, Tania -- Montalban, Xavier -- Mottershead, John -- Myhr, Kjell-Morten -- Naldi, Paola -- Ollier, William -- Page, Alison -- Palotie, Aarno -- Pelletier, Jean -- Piccio, Laura -- Pickersgill, Trevor -- Piehl, Fredrik -- Pobywajlo, Susan -- Quach, Hong L -- Ramsay, Patricia P -- Reunanen, Mauri -- Reynolds, Richard -- Rioux, John D -- Rodegher, Mariaemma -- Roesner, Sabine -- Rubio, Justin P -- Ruckert, Ina-Maria -- Salvetti, Marco -- Salvi, Erika -- Santaniello, Adam -- Schaefer, Catherine A -- Schreiber, Stefan -- Schulze, Christian -- Scott, Rodney J -- Sellebjerg, Finn -- Selmaj, Krzysztof W -- Sexton, David -- Shen, Ling -- Simms-Acuna, Brigid -- Skidmore, Sheila -- Sleiman, Patrick M A -- Smestad, Cathrine -- Sorensen, Per Soelberg -- Sondergaard, Helle Bach -- Stankovich, Jim -- Strange, Richard C -- Sulonen, Anna-Maija -- Sundqvist, Emilie -- Syvanen, Ann-Christine -- Taddeo, Francesca -- Taylor, Bruce -- Blackwell, Jenefer M -- Tienari, Pentti -- Bramon, Elvira -- Tourbah, Ayman -- Brown, Matthew A -- Tronczynska, Ewa -- Casas, Juan P -- Tubridy, Niall -- Corvin, Aiden -- Vickery, Jane -- Jankowski, Janusz -- Villoslada, Pablo -- Markus, Hugh S -- Wang, Kai -- Mathew, Christopher G -- Wason, James -- Palmer, Colin N A -- Wichmann, H-Erich -- Plomin, Robert -- Willoughby, Ernest -- Rautanen, Anna -- Winkelmann, Juliane -- Wittig, Michael -- Trembath, Richard C -- Yaouanq, Jacqueline -- Viswanathan, Ananth C -- Zhang, Haitao -- Wood, Nicholas W -- Zuvich, Rebecca -- Deloukas, Panos -- Langford, Cordelia -- Duncanson, Audrey -- Oksenberg, Jorge R -- Pericak-Vance, Margaret A -- Haines, Jonathan L -- Olsson, Tomas -- Hillert, Jan -- Ivinson, Adrian J -- De Jager, Philip L -- Peltonen, Leena -- Stewart, Graeme J -- Hafler, David A -- Hauser, Stephen L -- McVean, Gil -- Donnelly, Peter -- Compston, Alastair -- 068545/Z/02/Wellcome Trust/United Kingdom -- 075491/Z/04/Z/Wellcome Trust/United Kingdom -- 084702/Wellcome Trust/United Kingdom -- 085475/Wellcome Trust/United Kingdom -- 085475/B/08/Z/Wellcome Trust/United Kingdom -- 085475/Z/08/Z/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 898/Multiple Sclerosis Society/United Kingdom -- AI076544/AI/NIAID NIH HHS/ -- CA104021/CA/NCI NIH HHS/ -- G0100594/Medical Research Council/United Kingdom -- G0400017/Medical Research Council/United Kingdom -- G0700061/Medical Research Council/United Kingdom -- G0901310/Medical Research Council/United Kingdom -- G0901461/Medical Research Council/United Kingdom -- G19/2/Medical Research Council/United Kingdom -- K23N/S048869/PHS HHS/ -- NS032830/NS/NINDS NIH HHS/ -- NS049477/NS/NINDS NIH HHS/ -- NS049510/NS/NINDS NIH HHS/ -- NS067305/NS/NINDS NIH HHS/ -- NS19142/NS/NINDS NIH HHS/ -- NS26799/NS/NINDS NIH HHS/ -- NS43559/NS/NINDS NIH HHS/ -- PDA/02/06/016/Department of Health/United Kingdom -- R01 NS026799/NS/NINDS NIH HHS/ -- R01 NS049477/NS/NINDS NIH HHS/ -- R01 NS049477-06A1/NS/NINDS NIH HHS/ -- RR020092/RR/NCRR NIH HHS/ -- RR024992/RR/NCRR NIH HHS/ -- UL1 TR000448/TR/NCATS NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2011 Aug 10;476(7359):214-9. doi: 10.1038/nature10251.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21833088" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ban, Natalie C -- Caldwell, Iain R -- Green, Thomas L -- Morgan, Sian K -- O'Donnell, Kerrie -- Selgrath, Jennifer C -- New York, N.Y. -- Science. 2009 Jan 16;323(5912):338-9. doi: 10.1126/science.323.5912.338.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19150828" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sampson, Gabriel S -- Sanchirico, James N -- Roheim, Cathy A -- Bush, Simon R -- Taylor, J Edward -- Allison, Edward H -- Anderson, James L -- Ban, Natalie C -- Fujita, Rod -- Jupiter, Stacy -- Wilson, Jono R -- New York, N.Y. -- Science. 2015 May 1;348(6234):504-6. doi: 10.1126/science.aaa4639. Epub 2015 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of California, Davis, Davis, CA 95616, USA. ; University of California, Davis, Davis, CA 95616, USA. Resources for the Future, Washington, DC 20036, USA. jsanchirico@ucdavis.edu. ; University of Idaho, Moscow, ID 83844, USA. ; Wageningen University, Wageningen 6708 LX, Netherlands. ; University of Washington, Seattle, WA 98105, USA. ; University of Florida, Gainesville, FL 32611, USA. ; University of Victoria, Victoria, British Columbia V8W 2Y2, Canada. ; Environmental Defense Fund, San Francisco, CA 94105, USA. ; Wildlife Conservation Society, Suva, Fiji. ; The Nature Conservancy, Santa Barbara, CA 93106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25931542" target="_blank"〉PubMed〈/a〉

Description: Mammalian mitochondrial ribosomes (mitoribosomes) synthesize mitochondrially encoded membrane proteins that are critical for mitochondrial function. Here we present the complete atomic structure of the porcine 55S mitoribosome at 3.8 angstrom resolution by cryo-electron microscopy and chemical cross-linking/mass spectrometry. The structure of the 28S subunit in the complex was resolved at 3.6 angstrom resolution by focused alignment, which allowed building of a detailed atomic structure including all of its 15 mitoribosomal-specific proteins. The structure reveals the intersubunit contacts in the 55S mitoribosome, the molecular architecture of the mitoribosomal messenger RNA (mRNA) binding channel and its interaction with transfer RNAs, and provides insight into the highly specialized mechanism of mRNA recruitment to the 28S subunit. Furthermore, the structure contributes to a mechanistic understanding of aminoglycoside ototoxicity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Greber, Basil J -- Bieri, Philipp -- Leibundgut, Marc -- Leitner, Alexander -- Aebersold, Ruedi -- Boehringer, Daniel -- Ban, Nenad -- New York, N.Y. -- Science. 2015 Apr 17;348(6232):303-8. doi: 10.1126/science.aaa3872. Epub 2015 Apr 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Institute of Molecular Biology and Biophysics, Otto-Stern-Weg 5, ETH Zurich, CH-8093 Zurich, Switzerland. ; Department of Biology, Institute of Molecular Systems Biology, Auguste-Piccard-Hof 1, ETH Zurich, CH-8093 Zurich, Switzerland. ; Department of Biology, Institute of Molecular Systems Biology, Auguste-Piccard-Hof 1, ETH Zurich, CH-8093 Zurich, Switzerland. Faculty of Science, University of Zurich, CH-8057 Zurich, Switzerland. ; Department of Biology, Institute of Molecular Biology and Biophysics, Otto-Stern-Weg 5, ETH Zurich, CH-8093 Zurich, Switzerland. ban@mol.biol.ethz.ch.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25837512" target="_blank"〉PubMed〈/a〉

Description: Target of rapamycin (TOR), a conserved protein kinase and central controller of cell growth, functions in two structurally and functionally distinct complexes: TORC1 and TORC2. Dysregulation of mammalian TOR (mTOR) signaling is implicated in pathologies that include diabetes, cancer, and neurodegeneration. We resolved the architecture of human mTORC1 (mTOR with subunits Raptor and mLST8) bound to FK506 binding protein (FKBP)-rapamycin, by combining cryo-electron microscopy at 5.9 angstrom resolution with crystallographic studies of Chaetomium thermophilum Raptor at 4.3 angstrom resolution. The structure explains how FKBP-rapamycin and architectural elements of mTORC1 limit access to the recessed active site. Consistent with a role in substrate recognition and delivery, the conserved amino-terminal domain of Raptor is juxtaposed to the kinase active site.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aylett, Christopher H S -- Sauer, Evelyn -- Imseng, Stefan -- Boehringer, Daniel -- Hall, Michael N -- Ban, Nenad -- Maier, Timm -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):48-52. doi: 10.1126/science.aaa3870. Epub 2015 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland. ; Biozentrum, University of Basel, Basel, Switzerland. ; Biozentrum, University of Basel, Basel, Switzerland. ban@mol.biol.ethz.ch m.hall@unibas.ch timm.maier@unibas.ch. ; Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland. ban@mol.biol.ethz.ch m.hall@unibas.ch timm.maier@unibas.ch.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26678875" target="_blank"〉PubMed〈/a〉