6V4A

An open conformation of a Pentameic ligand-gated ion channel with additional N-terminal domain

Summary for 6V4A

• Entry DOI: 10.2210/pdb6v4a/pdb
• Descriptor: Neur_chan_LBD domain-containing protein, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, PHOSPHATIDYLGLYCEROL-PHOSPHOGLYCEROL (3 entities in total)
• Functional Keywords: pentameric ligand-gated ion channel, transport protein
• Biological source: uncultured Desulfofustis sp. PB-SRB1
• Total number of polymer chains: 5
• Total formula weight: 363645.66

Authors

Delarue, M.,Hu, H.D. (deposition date: 2019-11-27, release date: 2020-06-03, Last modification date: 2024-10-23)

Primary citation

Hu, H.,Howard, R.J.,Bastolla, U.,Lindahl, E.,Delarue, M.
Structural basis for allosteric transitions of a multidomain pentameric ligand-gated ion channel.
Proc.Natl.Acad.Sci.USA, 117:13437-13446, 2020

PubMed Abstract: Pentameric ligand-gated ion channels (pLGICs) are allosteric receptors that mediate rapid electrochemical signal transduction in the animal nervous system through the opening of an ion pore upon binding of neurotransmitters. Orthologs have been found and characterized in prokaryotes and they display highly similar structure-function relationships to eukaryotic pLGICs; however, they often encode greater architectural diversity involving additional amino-terminal domains (NTDs). Here we report structural, functional, and normal-mode analysis of two conformational states of a multidomain pLGIC, called DeCLIC, from a deltaproteobacterium, including a periplasmic NTD fused to the conventional ligand-binding domain (LBD). X-ray structure determination revealed an NTD consisting of two jelly-roll domains interacting across each subunit interface. Binding of Ca at the LBD subunit interface was associated with a closed transmembrane pore, with resolved monovalent cations intracellular to the hydrophobic gate. Accordingly, DeCLIC-injected oocytes conducted currents only upon depletion of extracellular Ca; these were insensitive to quaternary ammonium block. Furthermore, DeCLIC crystallized in the absence of Ca with a wide-open pore and remodeled periplasmic domains, including increased contacts between the NTD and classic LBD agonist-binding sites. Functional, structural, and dynamical properties of DeCLIC paralleled those of sTeLIC, a pLGIC from another symbiotic prokaryote. Based on these DeCLIC structures, we would reclassify the previous structure of bacterial ELIC (the first high-resolution structure of a pLGIC) as a "locally closed" conformation. Taken together, structures of DeCLIC in multiple conformations illustrate dramatic conformational state transitions and diverse regulatory mechanisms available to ion channels in pLGICs, particularly involving Ca modulation and periplasmic NTDs.

PubMed: 32482881
DOI: 10.1073/pnas.1922701117

Experimental method

X-RAY DIFFRACTION (3.83 Å)