生长抑素类似物，如奥曲肽（OCT）、兰瑞肽和帕瑞肽，作为生长抑素受体配体（SRL），是用于治疗肢端肥大症的主要药物。这些配体也用作神经内分泌肿瘤（NET）放射治疗和成像的重要分子。生长抑素受体 (SSTR) 是典型的 G 蛋白偶联蛋白 (GPCR)，在新陈代谢、生长和激素紊乱、神经系统疾病和癌症等病理状况中发挥作用。低温电子显微镜（cryo-EM）结合蛋白质结构预测平台AlphaFold已被用来确定许多蛋白质的三维结构。最近，几个小组发表了一系列论文，阐述了 SSTR2 的三维结构，包括与不同配体结合的失活/激活的 SSTR2-G 蛋白复合物的结构。结果揭示了有助于配体结合袋的残基，并证明生长抑素类似物中的Trp8-Lys9（W-K基序）是稳定结合袋底部的关键基序。在这篇综述中，我们讨论了与 SSTR 和 SRL 的结构分析相关的最新发现、结构数据与临床发现之间的关系，以及基于新型结构的疗法的未来发展。© 作者 2024。出版者牛津大学出版社代表内分泌学会。版权所有。如需商业重复使用，请联系 reprints@oup.com 获取转载和转载的翻译权。所有其他权限都可以通过我们网站文章页面上的权限链接通过我们的 RightsLink 服务获得 - 如需了解更多信息，请联系journals.permissions@oup.com。有关附加条款，请参阅期刊“关于”页面。

Somatostatin analogs, such as octreotide (OCT), lanreotide, and pasireotide, which function as somatostatin receptor ligands (SRLs), are the main drugs used for the treatment of acromegaly. These ligands are also used as important molecules for radiation therapy and imaging of neuroendocrine tumors (NETs). Somatostatin receptors (SSTRs) are canonical G protein-coupled proteins (GPCRs) that play a role in metabolism, growth, and pathological conditions such as hormone disorders, neurological diseases, and cancers. Cryogenic electron microscopy (cryo-EM) combined with the protein structure prediction platform AlphaFold has been used to determine the three-dimensional structures of many proteins. Recently, several groups published a series of papers illustrating the three-dimensional structure of SSTR2, including that of the inactive/activated SSTR2-G protein complex bound to different ligands. The results revealed the residues that contribute to the ligand binding pocket and demonstrated that Trp8-Lys9 (the W-K motif) in somatostatin analogs is the key motif in stabilizing the bottom part of the binding pocket. In this review, we discuss the recent findings related to the structural analysis of SSTRs and SRLs, the relationships between the structural data and clinical findings, and the future development of novel structure-based therapies.© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.