Sialic acid mediated mechanical activation of β2 adrenergic receptors by bacterial pili

Zoe Virion, Stéphane Doly, Kusumika Saha, Mireille Lambert, François Guillonneau, Camille Bied, Rebecca M. Duke, Pauline M. Rudd, Catherine Robbe-Masselot, Xavier Nassif, Mathieu Coureuil () and Stefano Marullo ()
Additional contact information
Zoe Virion: Université de Paris
Stéphane Doly: Université de Paris
Kusumika Saha: Université de Paris
Mireille Lambert: Université de Paris
François Guillonneau: Université de Paris
Camille Bied: Université de Paris
Rebecca M. Duke: Blackrock, Co.
Pauline M. Rudd: Blackrock, Co.
Catherine Robbe-Masselot: Université Lille
Xavier Nassif: Université de Paris
Mathieu Coureuil: Université de Paris
Stefano Marullo: Université de Paris

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Meningococcus utilizes β-arrestin selective activation of endothelial cell β2 adrenergic receptor (β2AR) to cause meningitis in humans. Molecular mechanisms of receptor activation by the pathogen and of its species selectivity remained elusive. We report that β2AR 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 β2AR 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.

Date: 2019
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DOI: 10.1038/s41467-019-12685-6

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