7T11

CryoEM structure of somatostatin receptor 2 in complex with Octreotide and Gi3.

7T11 の概要

• エントリーDOI: 10.2210/pdb7t11/pdb
• EMDBエントリー: 25587
• 分子名称: Guanine nucleotide-binding protein G(i) subunit alpha-3, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
• 機能のキーワード: gpcr, receptor, complex, membrane protein, membrane protein-signaling protein complex, membrane protein/signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 160707.77

構造登録者

Robertson, M.J.,Skinotis, G. (登録日: 2021-11-30, 公開日: 2022-03-09, 最終更新日: 2022-03-30)

主引用文献

Robertson, M.J.,Meyerowitz, J.G.,Panova, O.,Borrelli, K.,Skiniotis, G.
Plasticity in ligand recognition at somatostatin receptors.
Nat.Struct.Mol.Biol., 29:210-217, 2022

PubMed Abstract: Somatostatin is a signaling peptide that plays a pivotal role in physiologic processes relating to metabolism and growth through its actions at somatostatin receptors (SSTRs). Members of the SSTR subfamily, particularly SSTR2, are key drug targets for neuroendocrine neoplasms, with synthetic peptide agonists currently in clinical use. Here, we show the cryogenic-electron microscopy structures of active-state SSTR2 in complex with heterotrimeric G and either the endogenous ligand SST14 or the FDA-approved drug octreotide. Complemented by biochemical assays and molecular dynamics simulations, these structures reveal key details of ligand recognition and receptor activation at SSTRs. We find that SSTR ligand recognition is highly diverse, as demonstrated by ligand-induced conformational changes in ECL2 and substantial sequence divergence across subtypes in extracellular regions. Despite this complexity, we rationalize several known sources of SSTR subtype selectivity and identify an additional interaction for specific binding. These results provide valuable insights for structure-based drug discovery at SSTRs.

PubMed: 35210615
DOI: 10.1038/s41594-022-00727-5

実験手法

ELECTRON MICROSCOPY (2.7 Å)