title: The extracellular δ-domain is essential for the formation of CD81 tetraspanin webs.
abstract: CD81 is a ubiquitously expressed member of the tetraspanin family. It forms large molecular platforms, so-called tetraspanin webs that play physiological roles in a variety of cellular functions and are involved in viral and parasite infections. We have investigated which part of the CD81 molecule is required for the formation of domains in the cell membranes of T-cells and hepatocytes. Surprisingly, we find that large CD81 platforms assemble via the short extracellular δ-domain, independent from a strong primary partner binding and from weak interactions mediated by palmitoylation. The δ-domain is also essential for the platforms to function during viral entry. We propose that, instead of stable binary interactions, CD81 interactions via the small δ-domain, possibly involving a dimerization step, play the key role in organizing CD81 into large tetraspanin webs and controlling its function.
authors.affiliation: Department of Membrane Biochemistry, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Homsi
authors.affiliation: Department of Membrane Biochemistry, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
authors.forename: Jan-Gero
authors.initials: JG
authors.lastname: Schloetel
authors.affiliation: Department of Medical Microbiology and Hygiene, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Konstanze D
authors.initials: KD
authors.lastname: Scheffer
authors.affiliation: Department of Membrane Biochemistry, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Schmidt
authors.affiliation: Université Toulouse 3-Paul Sabatier, UPS, Laboratoire de Physique Théorique (IRSAMC), Toulouse, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Destainville
authors.affiliation: Department of Medical Microbiology and Hygiene, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Luise
authors.initials: L
authors.lastname: Florin
authors.affiliation: Department of Membrane Biochemistry, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany. Electronic address: thorsten.lang@uni-bonn.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Lang
mesh_terms: D056945:Hep G2 Cells; D006801:Humans; D019169:Jurkat Cells; D054878:Lipoylation; D011485:Protein Binding; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D060225:Tetraspanin 28 / Q000737:chemistry* / Q000378:metabolism
chemical_list: D060225:Tetraspanin 28