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About:
Implications for tetraspanin-enriched microdomain assembly based on structures of CD9 with EWI-F
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research paper
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Academic Article
research paper
schema:ScholarlyArticle
isDefinedBy
Covid-on-the-Web dataset
has title
Implications for tetraspanin-enriched microdomain assembly based on structures of CD9 with EWI-F
Creator
Van Bergen En Henegouwen, Paul
Doulkeridou, Sofia
Gros, Piet
Kroon-Batenburg, Loes
Lutz, Martin
Manshande, Jip
Neviani, Viviana
Oosterheert, Wout
Pearce, Nicholas
Pos, Wouter
Xenaki, Katerina
Source
BioRxiv
abstract
Tetraspanins are ubiquitous eukaryotic membrane proteins that contribute to a variety of signaling processes by spatially organizing partner-receptor molecules in the plasma membrane. How tetraspanins bind and cluster partner receptors into so-called tetraspanin-enriched microdomains is unknown. Here we present crystal structures of the large extracellular loop of CD9 in complex with nanobodies 4C8 and 4E8; and, the cryo-EM structure of 4C8-bound CD9 in complex with its prototypical partner EWI-F. The CD9 - EWI-F complex displays a tetrameric arrangement with two centrally positioned EWI-F molecules, dimerized through their ectodomains, and two CD9 molecules, one bound to each EWI-F single-pass transmembrane helix through CD9-helices h3 and h4. In the crystal structures, nanobodies 4C8 and 4E8 bind CD9 at the C and D loop, in agreement with 4C8 binding at the ends of the CD9 - EWI-F cryo-EM complex. Overall, the 4C8 - CD9 - EWI-F - EWI-F - CD9 - 4C8 complexes varied from nearly two-fold symmetric (i.e. with the two CD9 - 4C8 copies in nearly anti-parallel orientation) to ca. 50° bent arrangements. Since membrane helices h1 and h2 and the EC2 D-loop have been previously identified as sites for tetraspanin homo-dimerization, the observed linear but flexible arrangement of CD9 - EWI-F with potential CD9 - CD9 homo-dimerization at either end provides a new ‘concatenation model’ for forming short linear or circular assemblies, which may explain the occurrence of tetraspanin-enriched microdomains.
has issue date
2020-06-03
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bibo:doi
10.1101/2020.06.02.130047
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biorxiv
sha1sum (hex)
55e629e14908343aefb1479380a8dce6f07fbd84
schema:url
https://doi.org/10.1101/2020.06.02.130047
resource representing a document's title
Implications for tetraspanin-enriched microdomain assembly based on structures of CD9 with EWI-F
schema:publication
bioRxiv
resource representing a document's body
covid:55e629e14908343aefb1479380a8dce6f07fbd84#body_text
is
schema:about
of
named entity 'model'
named entity 'EC2'
named entity 'ends'
named entity 'D-loop'
named entity 'linear'
named entity 'orientation'
named entity 'positioned'
named entity 'CD9'
named entity 'observed'
named entity 'arrangements'
named entity 'bind'
named entity 'Overall'
named entity 'arrangement'
named entity 'linear'
named entity 'cryo-EM'
named entity 'CD9'
named entity 'complex'
named entity 'CD9'
named entity 'CD9'
named entity 'kDa'
named entity 'EWI'
named entity 'tetramer'
named entity 'C-terminal'
named entity 'cell cultures'
named entity 'CD9'
named entity 'EWI'
named entity 'TMDs'
named entity 'nanobodies'
named entity 'expression vector'
named entity 'image processing'
named entity 'fluorescence'
named entity 'Strep'
named entity 'co-purified'
named entity 'PCR'
named entity 'Tetraspanin'
named entity 'cryo-EM'
named entity 'CD9'
named entity 'conformational change'
named entity 'EWI'
named entity 'eluted'
named entity 'EWI'
named entity 'Nyquist frequency'
named entity 'Ig-like'
named entity 'hydrophobic interaction'
named entity 'CD9'
named entity 'EWI'
named entity 'micelle'
named entity 'EWI'
named entity 'integrins'
named entity 'cloned'
named entity 'EWI'
named entity 'digitonin'
named entity 'HEK293'
named entity 'CD9'
named entity 'colon'
named entity 'tetraspanin'
named entity 'EWI'
named entity 'Ig-like domains'
named entity '37°C'
named entity 'digitonin'
named entity 'EWI'
named entity 'Protein'
named entity 'tryptophan'
named entity 'nanobody'
named entity 'Trp'
named entity 'PHASER'
named entity 'R101'
named entity 'structural model'
named entity 'w/v'
named entity 'CD9'
named entity 'CD81'
named entity 'CD9'
named entity 'Nanobodies'
named entity 'CD81'
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