PlumX Metrics
Embed PlumX Metrics

Implications for tetraspanin-enriched microdomain assembly based on structures of CD9 with EWI-F

bioRxiv, ISSN: 2692-8205
2020
  • 2
    Citations
  • 0
    Usage
  • 0
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    2
    • Citation Indexes
      2
      • CrossRef
        2

Article Description

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. 50ºbent 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.

Bibliographic Details

Wout Oosterheert; Viviana Neviani; Jip Manshande; Nicholas M. Pearce; Loes M.J. Kroon-Batenburg; Martin Lutz; Piet Gros; Katerina T. Xenaki; Sofia Doulkeridou; Paul M.P. van Bergen en Henegouwen; Wouter Pos

Cold Spring Harbor Laboratory

Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Immunology and Microbiology; Neuroscience; Pharmacology, Toxicology and Pharmaceutics

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know