Structural basis for the inhibition of the chromatin repressor BAHD1 by the bacterial nucleomodulin LntA.

Abstract : The nucleus has emerged as a key target for nucleomodulins, a family of effectors produced by bacterial pathogens to control host transcription or other nuclear processes. The virulence factor LntA from Listeria monocytogenes stimulates interferon responses during infection by inhibiting BAHD1, a nuclear protein involved in gene silencing by promoting heterochromatin formation. So far, whether the interaction between LntA and BAHD1 is direct and sufficient for inhibiting BAHD1 activity is unknown. Here, we functionally characterized the molecular interface between the two proteins in vitro and in transfected or infected human cells. Based on the known tridimensional structure of LntA, we identified a dilysine motif (K180/K181) in the elbow region of LntA and a central proline-rich region in BAHD1 as crucial for the direct LntA-BAHD1 interaction. To better understand the role played by the dilysine motif in the functionality of LntA, we solved the crystal structure of a K180D/K181D mutant to a 2.2-Å resolution. This mutant highlights a drastic redistribution of surface charges in the vicinity of a groove, which likely plays a role in nucleomodulin target recognition. Mutation of the strategic dilysine motif also abolished the recruitment of LntA to BAHD1-associated nuclear foci and impaired the LntA-mediated stimulation of interferon responses upon infection. Last, the strict conservation of residues K180 and K181 in LntA sequences from 188 L. monocytogenes strains of different serotypes and origins further supports their functional importance. Together, these results provide structural and functional details about the mechanism of inhibition of an epigenetic factor by a bacterial nucleomodulin.
Liste complète des métadonnées

Littérature citée [32 références]  Voir  Masquer  Télécharger
Contributeur : Frank Thomas <>
Soumis le : lundi 26 janvier 2015 - 11:32:35
Dernière modification le : lundi 19 février 2018 - 14:34:04


Fichiers éditeurs autorisés sur une archive ouverte




Alice Lebreton, Viviana Job, Marie Ragon, Alban Le Monnier, Andréa Dessen, et al.. Structural basis for the inhibition of the chromatin repressor BAHD1 by the bacterial nucleomodulin LntA.. mBio, American Society for Microbiology, 2014, 5 (1), pp.e00775-13. 〈10.1128/mBio.00775-13〉. 〈hal-01109386〉



Consultations de la notice


Téléchargements de fichiers