6Z20

Structure of the EC2 domain of CD9 in complex with nanobody 4C8

Summary for 6Z20

• Entry DOI: 10.2210/pdb6z20/pdb
• Related: 6RLR 6Z1V 6Z1Z
• Descriptor: CD9 antigen, Nanobody 4C8, GLYCEROL, ... (5 entities in total)
• Functional Keywords: antibody-antigen complex, tetraspanin, cd9, ec2 domain, nanobody, cell adhesion
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 48659.79

Authors

Oosterheert, W.,Manshande, J.,Pearce, N.M.,Lutz, M.,Gros, P. (deposition date: 2020-05-14, release date: 2020-09-23, Last modification date: 2024-11-13)

Primary citation

Oosterheert, W.,Xenaki, K.T.,Neviani, V.,Pos, W.,Doulkeridou, S.,Manshande, J.,Pearce, N.M.,Kroon-Batenburg, L.M.,Lutz, M.,van Bergen En Henegouwen, P.M.,Gros, P.
Implications for tetraspanin-enriched microdomain assembly based on structures of CD9 with EWI-F.
Life Sci Alliance, 3:-, 2020

PubMed 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.

PubMed: 32958604
DOI: 10.26508/lsa.202000883

Experimental method

X-RAY DIFFRACTION (2.68 Å)