6m8s

Crystal structure of the KCTD12 H1 domain in complex with Gbeta1gamma2 subunitsCrystal structure of the KCTD12 H1 domain in complex with Gbeta1gamma2 subunits

Structural highlights 6m8s is a 15 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 3.71Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GBB1_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. 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. See Also GTP-binding protein 3D structures Transducin 3D structures

spinqualitylabelsall models 6m8s, resolution 3.71Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image