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Publication Abstract from PubMed

Tetraspanins are eukaryotic membrane proteins that contribute to a variety of signaling processes by organizing partner-receptor molecules in the plasma membrane. How tetraspanins bind and cluster partner receptors into tetraspanin-enriched microdomains is unknown. Here, we present crystal structures of the large extracellular loop of CD9 bound to nanobodies 4C8 and 4E8 and, the cryo-EM structure of 4C8-bound CD9 in complex with its partner EWI-F. CD9-EWI-F displays a tetrameric arrangement with two central EWI-F molecules, dimerized through their ectodomains, and two CD9 molecules, one bound to each EWI-F transmembrane helix through CD9-helices h3 and h4. In the crystal structures, nanobodies 4C8 and 4E8 bind CD9 at loops C and D, which is in agreement with the 4C8 conformation in the CD9-EWI-F complex. The complex varies from nearly twofold symmetric (with the two CD9 copies nearly anti-parallel) to ca. 50 degrees bent arrangements. This flexible arrangement of CD9-EWI-F with potential CD9 homo-dimerization at either end provides a "concatenation model" for forming short linear or circular assemblies, which may explain the occurrence of tetraspanin-enriched microdomains.

Implications for tetraspanin-enriched microdomain assembly based on structures of CD9 with EWI-F.,Oosterheert W, Xenaki KT, Neviani V, Pos W, Doulkeridou S, Manshande J, Pearce NM, Kroon-Batenburg LM, Lutz M, van Bergen En Henegouwen PM, Gros P Life Sci Alliance. 2020 Sep 21;3(11). pii: 3/11/e202000883. doi:, 10.26508/lsa.202000883. Print 2020 Nov. PMID:32958604^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.