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Article Dans Une Revue Scientific Reports Année : 2016

New Insights into Molecular Organization of Human Neuraminidase-1: Transmembrane Topology and Dimerization Ability

Pascal Maurice
Stéphanie Baud
Olga V Bocharova
  • Fonction : Auteur
Eduard V Bocharov
  • Fonction : Auteur
Charlotte Kawecki
Olivier Bocquet
  • Fonction : Auteur
Beatrice Romier
  • Fonction : Auteur
Laetitia Gorisse
  • Fonction : Auteur
Maxime Ghirardi
  • Fonction : Auteur
Laurent Duca
  • Fonction : Auteur
Sébastien Blaise
Laurent Martiny
  • Fonction : Auteur
Manuel Dauchez
Roman G Efremov
  • Fonction : Auteur
Laurent Debelle

Résumé

Neuraminidase 1 (NEU1) is a lysosomal sialidase catalyzing the removal of terminal sialic acids from sialyloconjugates. A plasma membrane-bound NEU1 modulating a plethora of receptors by desialylation, has been consistently documented from the last ten years. Despite a growing interest of the scientific community to NEU1, its membrane organization is not understood and current structural and biochemical data cannot account for such membrane localization. By combining molecular biology and biochemical analyses with structural biophysics and computational approaches, we identified here two regions in human NEU1-segments 139-159 (TM1) and 316-333 (TM2)-as potential transmembrane (TM) domains. In membrane mimicking environments, the corresponding peptides form stable α-helices and TM2 is suited for self-association. This was confirmed with full-size NEU1 by co-immunoprecipitations from membrane preparations and split-ubiquitin yeast two hybrids. The TM2 region was shown to be critical for dimerization since introduction of point mutations within TM2 leads to disruption of NEU1 dimerization and decrease of sialidase activity in membrane. In conclusion, these results bring new insights in the molecular organization of membrane-bound NEU1 and demonstrate, for the first time, the presence of two potential TM domains that may anchor NEU1 in the membrane, control its dimerization and sialidase activity.
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hal-02347486 , version 1 (05-11-2019)

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Pascal Maurice, Stéphanie Baud, Olga V Bocharova, Eduard V Bocharov, Andrey V. Kuznetsov, et al.. New Insights into Molecular Organization of Human Neuraminidase-1: Transmembrane Topology and Dimerization Ability. Scientific Reports, 2016, 6 (1), ⟨10.1038/srep38363⟩. ⟨hal-02347486⟩

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