6ssp

Structure of the pentameric ligand-gated ion channel ELIC in complex with a NAM nanobody

spinqualitylabelsall models 6ssp, resolution 3.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ssp is a 12 chain structure with sequence from Dickeya chrysanthemi and Lama glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.25Å Ligands: CA, UMQ Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ELIC_DICCH Publication Abstract from PubMed Pentameric ligand-gated ion channels (pLGICs) or Cys-loop receptors are involved in fast synaptic signaling in the nervous system. Allosteric modulators bind to sites that are remote from the neurotransmitter binding site, but modify coupling of ligand binding to channel opening. In this study, we developed nanobodies (single domain antibodies), which are functionally active as allosteric modulators, and solved co-crystal structures of the prokaryote (Erwinia) channel ELIC bound either to a positive or a negative allosteric modulator. The allosteric nanobody binding sites partially overlap with those of small molecule modulators, including a vestibule binding site that is not accessible in some pLGICs. Using mutagenesis, we extrapolate the functional importance of the vestibule binding site to the human 5-HT3 receptor, suggesting a common mechanism of modulation in this protein and ELIC. Thus we identify key elements of allosteric binding sites, and extend drug design possibilities in pLGICs with an accessible vestibule site. Modulation of the Erwinia ligand-gated ion channel (ELIC) and the 5-HT3 receptor via a common vestibule site.,Brams M, Govaerts C, Kambara K, Price KL, Spurny R, Gharpure A, Pardon E, Evans GL, Bertrand D, Lummis SC, Hibbs RE, Steyaert J, Ulens C Elife. 2020 Jan 28;9. pii: 51511. doi: 10.7554/eLife.51511. PMID:31990273 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ion channels 3D structures

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