publications

2022

1. Illumination of a progressive allosteric mechanism mediating the glycine receptor activation

   Sophie Shi, Solène N Lefebvre, Laurie Peverini, and 5 more authors

   bioRxiv 2022
2. Lateral fenestrations in the extracellular domain of the glycine receptor contribute to the main chloride permeation pathway

   Adrien H Cerdan, Laurie Peverini, Jean-Pierre Changeux, and 2 more authors

   Science Advances 2022

   Abs

   Glycine receptors (GlyRs) are ligand-gated ion channels mediating signal transduction at chemical synapses. Since the early patch-clamp electrophysiology studies, the details of the ion permeation mechanism have remained elusive. Here, we combine molecular dynamics simulations of a zebrafish GlyR-α1 model devoid of the intracellular domain with mutagenesis and single-channel electrophysiology of the full-length human GlyR-α1. We show that lateral fenestrations between subunits in the extracellular domain provide the main translocation pathway for chloride ions to enter/exit a central water-filled vestibule at the entrance of the transmembrane channel. In addition, we provide evidence that these fenestrations are at the origin of current rectification in known anomalous mutants and design de novo two inward-rectifying channels by introducing mutations within them. These results demonstrate the central role of lateral fenestrations on synaptic neurotransmission. Extracellular chloride ions access the glycine receptor pore via lateral fenestrations outdating the standard apical model.

2020

1. The glycine receptor allosteric ligands library (GRALL)

   Adrien H Cerdan, Marion Sisquellas, Gilberto Pereira, and 3 more authors

   Bioinformatics 2020
2. On the functional annotation of open-channel structures in the glycine receptor

   Adrien H Cerdan, and Marco Cecchini

   Structure 2020

2019

1. Exploring synaptic transmission and regulation in ionotropic receptors by molecular dynamics simulations and computational electrophysiology

   Adrien H Cerdan

   2019

2018

1. An ion-permeable state of the glycine receptor captured by molecular dynamics

   Adrien H Cerdan, Nicolas E Martin, and Marco Cecchini

   Structure 2018

2017

1. On the permeation of large organic cations through the pore of ATP-gated P2X receptors

   Mahboubi Harkat, Laurie Peverini, Adrien H Cerdan, and 8 more authors

   Proceedings of the National Academy of Sciences 2017
2. Privileged substructures to modulate protein–protein interactions

   Nicolas Bosc, Mélaine A Kuenemann, Jerome Bécot, and 3 more authors

   Journal of chemical information and modeling 2017

2016

1. Imbalance in chemical space: How to facilitate the identification of protein-protein interaction inhibitors

   Mélaine A Kuenemann, Céline M Labbé, Adrien H Cerdan, and 1 more author

   Scientific reports 2016