8yjp

Cryo-EM structure of human apo GPR156

spinqualitylabelsall models 8yjp, resolution 3.09Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8yjp is a 2 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: Electron Microscopy, Resolution 3.09Å Ligands: CLR, MW9 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GP156_HUMAN The disease is caused by variants affecting the gene represented in this entry. Function GP156_HUMAN Orphan G-protein coupled receptor involved in the regulation of hair cell orientation in mechanosensory organs of the inner ear. It is required to trigger a 180 degree reversal in hair cell orientation, creating a virtual line of polarity reversal (LPR) across which stereociliary bundles are arranged in opposite orientations.[UniProtKB:Q6PCP7] Publication Abstract from PubMed The class C orphan G-protein-coupled receptor (GPCR) GPR156, which lacks the large extracellular region, plays a pivotal role in auditory function through G(i2/3). Here, we firstly demonstrate that GPR156 with high constitutive activity is essential for maintaining auditory function, and further reveal the structural basis of the sustained role of GPR156. We present the cryo-EM structures of human apo GPR156 and the GPR156-G(i3) complex, unveiling a small extracellular region formed by extracellular loop 2 (ECL2) and the N-terminus. The GPR156 dimer in both apo state and G(i3) protein-coupled state adopt a transmembrane (TM)5/6-TM5/6 interface, indicating the high constitutive activity of GPR156 in the apo state. Furthermore, C-terminus in G-bound subunit of GPR156 plays a dual role in promoting G protein binding within G-bound subunit while preventing the G-free subunit from binding to additional G protein. Together, these results explain how GPR156 constitutive activity is maintained through dimerization and provide a mechanistic insight into the sustained role of GPR156 in maintaining auditory function. Molecular insights into the activation mechanism of GPR156 in maintaining auditory function.,Ma X, Chen LN, Liao M, Zhang L, Xi K, Guo J, Shen C, Shen DD, Cai P, Shen Q, Qi J, Zhang H, Zang SK, Dong YJ, Miao L, Qin J, Ji SY, Li Y, Liu J, Mao C, Zhang Y, Chai R Nat Commun. 2024 Dec 5;15(1):10601. doi: 10.1038/s41467-024-54681-5. PMID:39638804 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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