6a9x

Crystal Structure of AnkG/GABARAP ComplexCrystal Structure of AnkG/GABARAP Complex

Structural highlights 6a9x is a 2 chain structure with sequence from Mus musculus and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.202Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GBRAP_MOUSE Ubiquitin-like modifier that plays a role in intracellular transport of GABA(A) receptors and its interaction with the cytoskeleton. Involved in apoptosis. Involved in autophagy. Whereas LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation (By similarity). Publication Abstract from PubMed GABAergic circuits are critical for the synchronization and higher order function of brain networks. Defects in this circuitry are linked to neuropsychiatric diseases, including bipolar disorder, schizophrenia, and autism. Work in cultured neurons has shown that ankyrin-G plays a key role in the regulation of GABAergic synapses on the axon initial segment and somatodendritic domain of pyramidal neurons, where it interacts directly with the GABAA receptor-associated protein (GABARAP) to stabilize cell surface GABAA receptors. Here, we generated a knock-in mouse model expressing a mutation that abolishes the ankyrin-G/GABARAP interaction (Ank3 W1989R) to understand how ankyrin-G and GABARAP regulate GABAergic circuitry in vivo. We found that Ank3 W1989R mice exhibit a striking reduction in forebrain GABAergic synapses resulting in pyramidal cell hyperexcitability and disruptions in network synchronization. In addition, we identified changes in pyramidal cell dendritic spines and axon initial segments consistent with compensation for hyperexcitability. Finally, we identified the ANK3 W1989R variant in a family with bipolar disorder, suggesting a potential role of this variant in disease. Our results highlight the importance of ankyrin-G in regulating forebrain circuitry and provide novel insights into how ANK3 loss-of-function variants may contribute to human disease. Ankyrin-G regulates forebrain connectivity and network synchronization via interaction with GABARAP.,Nelson AD, Caballero-Floran RN, Rodriguez Diaz JC, Hull JM, Yuan Y, Li J, Chen K, Walder KK, Lopez-Santiago LF, Bennett V, McInnis MG, Isom LL, Wang C, Zhang M, Jones KS, Jenkins PM Mol Psychiatry. 2018 Nov 30. pii: 10.1038/s41380-018-0308-x. doi:, 10.1038/s41380-018-0308-x. PMID:30504823 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ankyrin 3D structures GABA receptor-associated protein 3D structures

spinqualitylabelsall models 6a9x, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image