6m8r

Crystal structure of the KCTD16 BTB domain in complex with GABAB2 peptide

spinqualitylabelsall models 6m8r, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6m8r is a 12 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.2Å Ligands: MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KCD16_HUMAN Auxiliary subunit of GABA-B receptors that determine the pharmacology and kinetics of the receptor response. Increases agonist potency and markedly alter the G-protein signaling of the receptors by accelerating onset and promoting desensitization (By similarity). Publication Abstract from PubMed The GABAB (gamma-aminobutyric acid type B) receptor is one of the principal inhibitory neurotransmitter receptors in the brain, and it signals through heterotrimeric G proteins to activate a variety of effectors, including G-protein-coupled inwardly rectifying potassium channels (GIRKs)(1,2). GABAB-receptor signalling is tightly regulated by auxiliary subunits called KCTDs, which control the kinetics of GIRK activation and desensitization(3-5). However, the mechanistic basis for KCTD modulation of GABAB signalling remains incompletely understood. Here, using a combination of X-ray crystallography, electron microscopy, and functional and biochemical experiments, we reveal the molecular details of KCTD binding to both GABAB receptors and G-protein betagamma subunits. KCTDs associate with the receptor by forming an asymmetric pentameric ring around a region of the receptor carboxy-terminal tail, while a second KCTD domain, H1, engages in a symmetric interaction with five copies of Gbetagamma in which the G-protein subunits also interact directly with one another. We further show that KCTD binding to Gbetagamma is highly cooperative, defining a model in which KCTD proteins cooperatively strip G proteins from GIRK channels to induce rapid desensitization following receptor activation. These results provide a framework for understanding the molecular basis for the precise temporal control of GABAB signalling by KCTD proteins. Structural basis for KCTD-mediated rapid desensitization of GABAB signalling.,Zheng S, Abreu N, Levitz J, Kruse AC Nature. 2019 Mar;567(7746):127-131. doi: 10.1038/s41586-019-0990-0. Epub 2019 Feb, 27. PMID:30814734 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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