Scholarlink

<p>G protein coupled receptors (GPCRs) mediate intracellular signaling by selectively activating heterotrimeric G proteins. While certain GPCRs exhibit a high specificity toward particular G protein subtypes, other GPCRs display promiscuous signaling by engaging interaction with multiple G protein families. Molecular determinants underlying the selectivity or promiscuity of the receptors remain incompletely understood. In the present study, we investigate various structural motifs within the intracellular domains of Muscarinic receptors to assess their role in both Gα subunit binding and activation. To this end, we generated chimeric receptors and applied both FRET- and BRET-based assays to monitor G protein binding and activation. Our study demonstrates that the determination of G protein coupling selectivity is not defined by single motifs or amino acids but rather by a complex interplay of various intracellular motifs affecting binding or/and subsequent activation. These results provide new insights into the structural basis of GPCR-G protein specificity.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A complex interplay of various intracellular motifs determines G protein binding and activation of muscarinic receptors

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月14日

查看全文
  • Sina B. Kirchhofer,
  • Volker Jelinek,
  • Katharina Klingelhöfer,
  • Anna-Lena Krett,
  • Moritz Bünemann

摘要

G protein coupled receptors (GPCRs) mediate intracellular signaling by selectively activating heterotrimeric G proteins. While certain GPCRs exhibit a high specificity toward particular G protein subtypes, other GPCRs display promiscuous signaling by engaging interaction with multiple G protein families. Molecular determinants underlying the selectivity or promiscuity of the receptors remain incompletely understood. In the present study, we investigate various structural motifs within the intracellular domains of Muscarinic receptors to assess their role in both Gα subunit binding and activation. To this end, we generated chimeric receptors and applied both FRET- and BRET-based assays to monitor G protein binding and activation. Our study demonstrates that the determination of G protein coupling selectivity is not defined by single motifs or amino acids but rather by a complex interplay of various intracellular motifs affecting binding or/and subsequent activation. These results provide new insights into the structural basis of GPCR-G protein specificity.