Structure of the Arabidopsis thaliana glutamate receptor-like channel GLR3.4

• Published in: Molecular cell Vol. 81; no. 15; pp. 3216 - 3226.e8
• Main Authors: Green, Marriah N., Gangwar, Shanti Pal, Michard, Erwan, Simon, Alexander A., Portes, Maria Teresa, Barbosa-Caro, Juan, Wudick, Michael M., Lizzio, Michael A., Klykov, Oleg, Yelshanskaya, Maria V., Feijó, José A., Sobolevsky, Alexander I.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 05.08.2021
• Subjects: Arabidopsis thaliana; cryo-EM; GLR; glutamate receptor; glutathione; glutathionylation; iGluR; plant; structure; X-ray crystallography; Arabidopsis thaliana; X-ray crystallography; iGluR; glutamate receptor; glutathionylation; glutathione; plant; GLR; cryo-EM; structure
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2021.05.025

Glutamate receptor-like channels (GLRs) play vital roles in various physiological processes in plants, such as wound response, stomatal aperture control, seed germination, root development, innate immune response, pollen tube growth, and morphogenesis. Despite the importance of GLRs, knowledge about their molecular organization is limited. Here we use X-ray crystallography and single-particle cryo-EM to solve structures of the Arabidopsis thaliana GLR3.4. Our structures reveal the tetrameric assembly of GLR3.4 subunits into a three-layer domain architecture, reminiscent of animal ionotropic glutamate receptors (iGluRs). However, the non-swapped arrangement between layers of GLR3.4 domains, binding of glutathione through S-glutathionylation of cysteine C205 inside the amino-terminal domain clamshell, unique symmetry, inter-domain interfaces, and ligand specificity distinguish GLR3.4 from representatives of the iGluR family and suggest distinct features of the GLR gating mechanism. Our work elaborates on the principles of GLR architecture and symmetry and provides a molecular template for deciphering GLR-dependent signaling mechanisms in plants. [Display omitted] •Cryo-EM structure of Arabidopsis thaliana glutamate receptor-like channel GLR3.4•Glutathione regulates channel activity by binding to C205 in amino-terminal domain•Crystal structures of GLR3.4 ligand-binding domain illustrate ligand promiscuity•Amino-terminal and ligand-binding domain layers show non-swapped domain arrangement Green et al. solve structures of Arabidopsis thaliana glutamate receptor-like channel GLR3.4 that shows tetrameric subunit assembly with three-layer architecture, similar to its mammalian homologs, ionotropic glutamate receptors, but with distinct symmetry, inter-domain interfaces, ligand specificity, and non-swapped domain arrangement between layers of ligand-binding and glutathione-bound amino-terminal domains.