Rxivist logo

Mechanisms of activation and desensitization of full-length glycine receptor in membranes

By Arvind Kumar, Sandip Basak, Shanlin Rao, Yvonne Gicheru, Megan L Mayer, Mark S.P. Sansom, Sudha Chakrapani

Posted 30 Sep 2019
bioRxiv DOI: 10.1101/788695 (published DOI: 10.1016/j.bpj.2019.11.1159)

Glycinergic synapses play a central role in motor control and pain processing in the central nervous system. Glycine receptors (GlyR) are key players in mediating fast inhibitory neurotransmission at these synapses. While previous high-resolution structural studies have provided insights into the molecular architecture of GlyR, several mechanistic questions pertaining to channel function are still unknown. Here, we present Cryo-EM structures of the full-length GlyR protein reconstituted into lipid nanodiscs that are captured in the unliganded (closed) and glycine-bound (open and desensitized) conformations. A comparison of the three states reveals global conformational changes underlying GlyR channel gating. The functional state assignments were validated by molecular dynamics simulations of the structures incorporated in a lipid bilayer. Observed permeation events are in agreement with the anion selectivity of the channel and the reported single-channel conductance of GlyR. These studies establish the structural basis for gating, selectivity, and single-channel conductance of GlyR in a physiological environment.

Download data

  • Downloaded 970 times
  • Download rankings, all-time:
    • Site-wide: 12,860 out of 94,912
    • In biophysics: 407 out of 4,144
  • Year to date:
    • Site-wide: 8,097 out of 94,912
  • Since beginning of last month:
    • Site-wide: 10,313 out of 94,912

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News