Structural insights into the activation of somatostatin receptor 2 by cyclic SST analogues

• DOI: 10.1038/s41421-022-00405-2
• Publication Date: 2022-05-20T07:03:07Z
• Authors: Qing Bo; Fan Yang; Yingge Li; Xianyu Meng; Huanhuan Zhang; Yingxin Zhou; Shenglong Ling; Demeng Sun; Pei Lv; Lei Liu; Pan Shi; Changlin Tian
• Keywords: 0303 health sciences; 03 medical and health sciences; QH573-671; Cytology; Article; 3. Good health

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 SST analogues (lanreotide or octreotide) with improved stability longer lifetime were developed as drugs preferentially activate SSTR2 treat acromegalia neuroendocrine tumors. Here, cryo-EM structures of the human SSTR2-Gi complex bound SST14, octreotide lanreotide determined at resolutions 2.85 Å, 2.97 2.87 respectively. Structural functional analysis revealed that interactions between β-turn residues in transmembrane ligand-binding pocket are crucial receptor binding stimulation two octapeptides. Additionally, Q102