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Structural Bases for Tetraspanin Functions

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Tetraspanins

Part of the book series: Proteins and Cell Regulation ((PROR,volume 9))

Abstract

The tetraspanin transmembrane glycoproteins are considered as “molecular facilitators” which simultaneously interact with, and thereby bring into close proximity specific proteins involved in cellular activation and transduction processes. Elucidation of the 3D structure of tetraspanins is an essential step in understanding of their facilitator function and of the molecular basis of their partner specificity. Although there are currently no experimental atomic resolution structures of a whole tetraspanin molecule, recent information gained from three different approaches has led to a rather comprehensive picture of the structural organization of tetraspanins. These include: (1) crystallographic structures of the main extracellular domain of the ubiquitous tetraspanin CD81; (2) a 6 Å-resolution cryo-EM structure of the tetraspanins uroplakin UPIa and UPIb in the urothelial plaque of mammalian urothelium; (3) molecular modeled-structures of the complete CD81 tetraspanin. On the basis of such structural data, a qualitative view of tetraspanin structure-function relationship is emerging, including a delineation of regions of the molecule involved in specific interactions with partners, as well as an understanding of the structural basis of the multilevel partner specificity of tetraspanins and of the tetraspanin network organization.

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Abbreviations

AUM:

Asymmetric unit membrane (AUM)

Cryo-EM:

Cryo-electron microscopy

EC1:

First tetraspanin extracellular region

EC2:

Second tetraspanin extracellular region

EM:

Electron microscopy

IC:

Intracellular

TEM:

Tetraspanin-enriched microdomain

TM:

Transmembrane

UP:

Uroplakin

UPEC:

Uropathogenic E. coli

UPIa:

Uroplakin Ia

UPIb:

Uroplakin Ib

UPII:

Uroplakin II

UPIIIa:

Uroplakin IIIa

UTI:

Urinary tract infection

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Acknowledgments

The work done in the authors’ laboratories was supported by grants from the Centre National de la Recherche Scientifique, the Institut National de la Santé et de la Recherche Médicale, SIDACTION, the Association National pour la Recherche Contre le SIDA (to HC and MS) and NIH grant DK52206 (to HTZ and XPK).

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Authors and Affiliations

  1. Matière et Systèmes Complexes – CNRS UMR 7057, Université Paris-Diderot, 10 rue Alice Domon et Léonie Duquet, Paris cedex 13, 75205, France

    Michel Seigneuret & Hélène Conjeaud

  2. Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA

    Hui-Tang Zhang & Xiang-Peng Kong

Authors
  1. Michel Seigneuret
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  2. Hélène Conjeaud
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  3. Hui-Tang Zhang
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  4. Xiang-Peng Kong
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Correspondence to Michel Seigneuret .

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Editors and Affiliations

  1. , School of Cancer Sciences, University of Birmingham, Vincent Drive, Birmingham, B15 2TT, United Kingdom

    Fedor Berditchevski

  2. INSERM U1004, Av. Paul Vaillant Couturier 14, Villejuif, F-94807, France

    Eric Rubinstein

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Seigneuret, M., Conjeaud, H., Zhang, HT., Kong, XP. (2013). Structural Bases for Tetraspanin Functions. In: Berditchevski, F., Rubinstein, E. (eds) Tetraspanins. Proteins and Cell Regulation, vol 9. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6070-7_1

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