Sialic acid mediated mechanical activation of β 2 adrenergic receptors by bacterial pili - Archive ouverte HAL
Article Dans Une Revue Nature Communications Année : 2019

Sialic acid mediated mechanical activation of β 2 adrenergic receptors by bacterial pili

Résumé

Meningococcus utilizes β-arrestin selective activation of endothelial cell β 2 adrenergic receptor (β 2 AR) to cause meningitis in humans. Molecular mechanisms of receptor activation by the pathogen and of its species selectivity remained elusive. We report that β 2 AR activation requires two asparagine-branched glycan chains with terminally exposed N-acetyl-neuraminic acid (sialic acid, Neu5Ac) residues located at a specific distance in its N-terminus, while being independent of surrounding amino-acid residues. Meningococcus triggers receptor signaling by exerting direct and hemodynamic-promoted traction forces on β 2 AR glycans. Similar activation is recapitulated with beads coated with Neu5Ac-binding lectins, submitted to mechanical stimulation. This previously unknown glycan-dependent mode of allosteric mechanical activation of a G protein-coupled receptor contributes to meningococcal species selectivity, since Neu5Ac is only abundant in humans due to the loss of CMAH, the enzyme converting Neu5Ac into N-glycolyl-neuraminic acid in other mammals. It represents an additional mechanism of evolutionary adaptation of a pathogen to its host.

Domaines

Bactériologie
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Dates et versions

hal-02485670 , version 1 (20-02-2020)

Identifiants

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Zoé Virion, Stéphane Doly, Kusumika Saha, Mireille Lambert, Francois Guillonneau, et al.. Sialic acid mediated mechanical activation of β 2 adrenergic receptors by bacterial pili. Nature Communications, 2019, 10, pp.4752. ⟨10.1038/s41467-019-12685-6⟩. ⟨hal-02485670⟩
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