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dc.contributor.authorKelly, Deborah F.en
dc.contributor.authorLake, Robert J.en
dc.contributor.authorMiddelkoop, Teije C.en
dc.contributor.authorFan, Hua-Yingen
dc.contributor.authorArtavanis-Tsakonas, Spyrosen
dc.contributor.authorWalz, Thomasen
dc.coverage.spatialUnited Statesen
dc.date.accessioned2018-02-12T15:57:22Zen
dc.date.available2018-02-12T15:57:22Zen
dc.date.issued2010-05-07en
dc.identifier.urihttp://hdl.handle.net/10919/82063en
dc.description.abstractBACKGROUND: The Notch receptor links cell fate decisions of one cell to that of the immediate cellular neighbor. In humans, malfunction of Notch signaling results in diseases and congenital disorders. Structural information is essential for gaining insight into the mechanism of the receptor as well as for potentially interfering with its function for therapeutic purposes. METHODOLOGY/PRINCIPAL FINDINGS: We used the Affinity Grid approach to prepare specimens of the Notch extracellular domain (NECD) of the Drosophila Notch and human Notch1 receptors suitable for analysis by electron microscopy and three-dimensional (3D) image reconstruction. The resulting 3D density maps reveal that the NECD structure is conserved across species. We show that the NECD forms a dimer and adopts different yet defined conformations, and we identify the membrane-proximal region of the receptor and its ligand-binding site. CONCLUSIONS/SIGNIFICANCE: Our results provide direct and unambiguous evidence that the NECD forms a dimer. Our studies further show that the NECD adopts at least three distinct conformations that are likely related to different functional states of the receptor. These findings open the way to now correlate mutations in the NECD with its oligomeric state and conformation.en
dc.format.extente10532 - ? page(s)en
dc.languageengen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/20479883en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectAnimalsen
dc.subjectDrosophila melanogasteren
dc.subjectExtracellular Spaceen
dc.subjectHumansen
dc.subjectMicroscopy, Electronen
dc.subjectProtein Multimerizationen
dc.subjectProtein Structure, Tertiaryen
dc.subjectReceptors, Notchen
dc.titleMolecular structure and dimeric organization of the Notch extracellular domain as revealed by electron microscopy.en
dc.typeArticle - Refereeden
dc.description.versionPublished online (Publication status)en
dc.title.serialPLoS Oneen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0010532en
dc.type.otherJournal Articleen
dc.type.otherResearch Support, N.I.H., Extramuralen
dc.type.otherResearch Support, Non-U.S. Gov'ten
dc.identifier.volume5en
dc.identifier.issue5en
dc.identifier.orcidKelly, DF [0000-0002-7341-7435]en
dcterms.dateAccepted2010-04-16en
dc.identifier.eissn1932-6203en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Virginia Tech Carilion Research Instituteen


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