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Implications for tetraspanin-enriched microdomain assembly based on structures of CD9 with EWI-F
Authors:
Wout
Oosterheert
(Utrecht University)
,
Katerina T.
Xenaki
(Utrecht University)
,
Viviana
Neviani
(Utrecht University)
,
Wouter
Pos
(uniQure Biopharma)
,
Sofia
Doulkeridou
(Utrecht University)
,
Jip
Manshande
(Utrecht University)
,
Nicholas M.
Pearce
(Utrecht University)
,
Loes M. J.
Kroon-Batenburg
(Utrecht University)
,
Martin
Lutz
(Utrecht University)
,
Paul M. P.
Van Bergen En Henegouwen
(Utrecht University)
,
Piet
Gros
(Utrecht University)
Co-authored by industrial partner:
Yes
Type:
Journal Paper
Journal:
Life Science Alliance
, VOL 3
State:
Published (Approved)
Published:
September 2020
Diamond Proposal Number(s):
19800

Abstract: 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° 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.
Subject Areas:
Biology and Bio-materials,
Chemistry
Instruments:
I03-Macromolecular Crystallography
,
I04-1-Macromolecular Crystallography (fixed wavelength)
Other Facilities: ID23-2 at ESRF
Added On:
23/09/2020 09:38
Documents:
e202000883.full.pdf
Discipline Tags:
Biochemistry
Chemistry
Structural biology
Life Sciences & Biotech
Technical Tags:
Diffraction
Macromolecular Crystallography (MX)