7xav

Structure of somatostatin receptor 2 bound with lanreotide.

spinqualitylabelsall models 7xav, resolution 2.87Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7xav is a 6 chain structure with sequence from Bos taurus, Homo sapiens, Rattus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.87Å Ligands: 4J2, DTR, NH2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GBB1_BOVIN 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 endogenous cyclic tetradecapeptide SST14 was reported to stimulate all five somatostatin receptors (SSTR1-5) for hormone release, neurotransmission, cell growth arrest and cancer suppression. Two SST14-derived short cyclic SST analogues (lanreotide or octreotide) with improved stability and longer lifetime were developed as drugs to preferentially activate SSTR2 and treat acromegalia and neuroendocrine tumors. Here, cryo-EM structures of the human SSTR2-Gi complex bound with SST14, octreotide or lanreotide were determined at resolutions of 2.85 A, 2.97 A, and 2.87 A, respectively. Structural and functional analysis revealed that interactions between beta-turn residues in SST analogues and transmembrane SSTR2 residues in the ligand-binding pocket are crucial for receptor binding and functional stimulation of the two SST14-derived cyclic octapeptides. Additionally, Q102(2.63), N276(6.55), and F294(7.35) could be responsible for the selectivity of lanreotide or octreotide for SSTR2 over SSTR1 or SSTR4. These results provide valuable insights into further rational development of SST analogue drugs targeting SSTR2. Structural insights into the activation of somatostatin receptor 2 by cyclic SST analogues.,Bo Q, Yang F, Li Y, Meng X, Zhang H, Zhou Y, Ling S, Sun D, Lv P, Liu L, Shi P, Tian C Cell Discov. 2022 May 20;8(1):47. doi: 10.1038/s41421-022-00405-2. PMID:35595746 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transducin 3D structures

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