6cdu

Crystal structure of a chimeric human alpha1GABAA receptor in complex with alphaxaloneCrystal structure of a chimeric human alpha1GABAA receptor in complex with alphaxalone

Structural highlights 6cdu is a 10 chain structure with sequence from Dickeya dadantii 3937 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.45Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GBRA1_HUMAN Juvenile myoclonic epilepsy;Childhood absence epilepsy;Dravet syndrome. Disease susceptibility is associated with variations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function E0SJQ4_DICD3 GBRA1_HUMAN Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity). Publication Abstract from PubMed Type A gamma-aminobutyric acid receptors (GABAARs) are inhibitory pentameric ligand-gated ion channels in the brain. Many anesthetics and neurosteroids act through binding to the GABAAR transmembrane domain (TMD), but the structural basis of their actions is not well understood and no resting-state GABAAR structure has been determined. Here, we report crystal structures of apo and the neurosteroid anesthetic alphaxalone-bound desensitized chimeric alpha1GABAAR (ELIC-alpha1GABAAR). The chimera retains the functional and pharmacological properties of GABAARs, including potentiation, activation and desensitization by alphaxalone. The apo-state structure reveals an unconventional activation gate at the intracellular end of the pore. The desensitized structure illustrates molecular determinants for alphaxalone binding to an inter-subunit TMD site. These structures suggest a plausible signaling pathway from alphaxalone binding at the bottom of the TMD to the channel gate in the pore-lining TM2 through the TM1-TM2 linker. The study provides a framework to discover new GABAAR modulators with therapeutic potential. Structural basis of neurosteroid anesthetic action on GABAA receptors.,Chen Q, Wells MM, Arjunan P, Tillman TS, Cohen AE, Xu Y, Tang P Nat Commun. 2018 Sep 28;9(1):3972. doi: 10.1038/s41467-018-06361-4. PMID:30266951 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also GABA receptor 3D structures

spinqualitylabelsall models 6cdu, resolution 3.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image