6ibl

ACTIVATED TURKEY BETA1 ADRENOCEPTOR WITH BOUND AGONIST FORMOTEROL AND NANOBODY Nb80

spinqualitylabelsall models 6ibl, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ibl is a 4 chain structure with sequence from Escherichia coli K-12, Lama glama and Meleagris gallopavo. This structure supersedes the now removed PDB entry 6h7k. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Ligands: 2CV, H98, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function THIO_ECOLI Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions.ADRB1_MELGA Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Publication Abstract from PubMed The beta1-adrenoceptor (beta1AR) is a G-protein-coupled receptor (GPCR) that couples(1) to the heterotrimeric G protein Gs. G-protein-mediated signalling is terminated by phosphorylation of the C terminus of the receptor by GPCR kinases (GRKs) and by coupling of beta-arrestin 1 (betaarr1, also known as arrestin 2), which displaces Gs and induces signalling through the MAP kinase pathway(2). The ability of synthetic agonists to induce signalling preferentially through either G proteins or arrestins-known as biased agonism(3)-is important in drug development, because the therapeutic effect may arise from only one signalling cascade, whereas the other pathway may mediate undesirable side effects(4). To understand the molecular basis for arrestin coupling, here we determined the cryo-electron microscopy structure of the beta1AR-betaarr1 complex in lipid nanodiscs bound to the biased agonist formoterol(5), and the crystal structure of formoterol-bound beta1AR coupled to the G-protein-mimetic nanobody(6) Nb80. betaarr1 couples to beta1AR in a manner distinct to that(7) of Gs coupling to beta2AR-the finger loop of betaarr1 occupies a narrower cleft on the intracellular surface, and is closer to transmembrane helix H7 of the receptor when compared with the C-terminal alpha5 helix of Gs. The conformation of the finger loop in betaarr1 is different from that adopted by the finger loop of visual arrestin when it couples to rhodopsin(8). beta1AR coupled to betaarr1 shows considerable differences in structure compared with beta1AR coupled to Nb80, including an inward movement of extracellular loop 3 and the cytoplasmic ends of H5 and H6. We observe weakened interactions between formoterol and two serine residues in H5 at the orthosteric binding site of beta1AR, and find that formoterol has a lower affinity for the beta1AR-betaarr1 complex than for the beta1AR-Gs complex. The structural differences between these complexes of beta1AR provide a foundation for the design of small molecules that could bias signalling in the beta-adrenoceptors. Molecular basis of beta-arrestin coupling to formoterol-bound beta1-adrenoceptor.,Lee Y, Warne T, Nehme R, Pandey S, Dwivedi-Agnihotri H, Chaturvedi M, Edwards PC, Garcia-Nafria J, Leslie AGW, Shukla AK, Tate CG Nature. 2020 Jun 17. pii: 10.1038/s41586-020-2419-1. doi:, 10.1038/s41586-020-2419-1. PMID:32555462 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Adrenergic receptor 3D structures Antibody 3D structures 3D structures of non-human antibody

Proteopedia Page Contributors and Editors (what is this?)

OCA