8pm2

Structure of the murine trace amine-associated receptor TAAR7f bound to N,N-dimethylcyclohexylamine (DMCH) in complex with mini-Gs trimeric G proteinStructure of the murine trace amine-associated receptor TAAR7f bound to N,N-dimethylcyclohexylamine (DMCH) in complex with mini-Gs trimeric G protein

Structural highlights 8pm2 is a 5 chain structure with sequence from Homo sapiens, Lama glama and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.92Å Ligands: , 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 There are two main families of G protein-coupled receptors that detect odours in humans, the odorant receptors (ORs) and the trace amine-associated receptors (TAARs). Their amino acid sequences are distinct, with the TAARs being most similar to the aminergic receptors such as those activated by adrenaline, serotonin and histamine. To elucidate the structural determinants of ligand recognition by TAARs, we have determined the cryo-EM structure of a murine receptor, mTAAR7f, coupled to the heterotrimeric G protein G (s) and bound to the odorant N,N-dimethylcyclohexylamine (DMCH) to an overall resolution of 2.9 A. DMCH is bound in a hydrophobic orthosteric binding site primarily through van der Waals interactions and a strong charge-charge interaction between the tertiary amine of the ligand and an aspartic acid residue. This site is distinct and non-overlapping with the binding site for the odorant propionate in the odorant receptor OR51E2. The structure, in combination with mutagenesis data and molecular dynamics simulations suggests that the activation of the receptor follows a similar pathway to that of the beta-adrenoceptors, with the significant difference that DMCH interacts directly with one of the main activation microswitch residues. Molecular recognition of an aversive odorant by the murine trace amine-associated receptor TAAR7f.,Gusach A, Lee Y, Khoshgrudi AN, Mukhaleva E, Ma N, Koers EJ, Chen Q, Edwards PC, Huang F, Kim J, Mancia F, Verprintsev DB, Vaidehi N, Weyand SN, Tate CG bioRxiv. 2023 Jul 7:2023.07.07.547762. doi: 10.1101/2023.07.07.547762. Preprint. PMID:37461561 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 8pm2, resolution 2.92Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image