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Updated: Feb 13, 2026

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

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Published on: May 20, 2020

ソマトスタチン受容体3のリガンド認識と活性化に関する構造的および動的洞察

Xue Chen^1,2, Sen Guo^1,2, Ying-Ge Li^1,2

¹School of Life Sciences, Division of Life Sciences and Medicine, Joint Center for Biological Analytical Chemistry, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230026, China.

Acta pharmacologica Sinica

|February 11, 2026

Abstract:

Somatostatin receptor 3 (SSTR3) exerts critical biological functions such as negatively regulating hormone release and cell proliferation, making it a promising therapeutic target for endocrine disorders and nonfunctioning pituitary tumors. However, the development of more effective and safer somatostatinergic therapies is limited due to a lack of molecular understanding of the ligand recognition and conformational dynamics of SSTR3. Here, we report the cryo-EM structure of the human SSTR3-Gi complex bound to octreotide at 2.90 Å resolution. Our structures reveal the molecular mechanisms of ligand recognition and receptor activation. Furthermore, mutagenesis analyses reveal that residue R203⁵·³⁵ of SSTR3 and F294⁷·³⁵ of SSTR2 play critical roles in mediating the subtype selectivity of octreotide. Using electron paramagnetic resonance spectroscopy, we have investigated the conformational dynamics of SSTR3. Our findings demonstrate that during ligand binding or G protein coupling, the labeled site on transmembrane helix 6 (TM6) of SSTR3 progressively becomes exposed to the extracellular environment and exhibits increased dynamical characteristics. Our work provides structural and dynamic insights that will facilitate the rational design of subtype-selective drugs targeting SSTRs and possessing improved therapeutic profiles.

キーワード:

ソマトスタチン受容体3 クライオ電子顕微鏡電子常磁性共鳴分光法オクトレオチド

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