Scholarlink

<p>G protein coupled receptors (GPCRs) oligomerization may allow signal integration from different GPCR units. The GABA<sub>B</sub> receptor, activated by the main inhibitory transmitter, GABA, is an obligatory heterodimer. It is the target of two therapeutic drugs, baclofen and GHB, and can form stable oligomers. The existence, roles, and possible allosteric interaction of GABA<sub>B</sub> oligomers remain elusive. Here, we show that GABA<sub>B</sub> oligomers exist in neurons. Their function can be specifically affected by human disease-associated mutations, demonstrating their essential role for normal brain function. The cryo-EM structure of a hetero-tetramer in the apo state reveals the heterodimers interacting in an asymmetrical way to prevent one unit from being activated. This represents a nice example of a negative allosteric interaction between GPCRs related to human diseases.</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

Functional and structural basis of a negative allostery within GABAB hetero-tetramers

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月20日

查看全文
  • Cangsong Shen,
  • Hongyang Ding,
  • Shenlan Zhang,
  • Chanjuan Xu,
  • Binqian Zou,
  • Suyu Ji,
  • Yi-Ru Liu,
  • Yizhong Li,
  • Rui Zhou,
  • Jiayin Liang,
  • Dan-dan Shen,
  • Yuxuan Liu,
  • Xuan Chen,
  • Philippe Rondard,
  • Jun He,
  • Yan Zhang,
  • Jean-Philippe Pin,
  • Jianfeng Liu

摘要

G protein coupled receptors (GPCRs) oligomerization may allow signal integration from different GPCR units. The GABAB receptor, activated by the main inhibitory transmitter, GABA, is an obligatory heterodimer. It is the target of two therapeutic drugs, baclofen and GHB, and can form stable oligomers. The existence, roles, and possible allosteric interaction of GABAB oligomers remain elusive. Here, we show that GABAB oligomers exist in neurons. Their function can be specifically affected by human disease-associated mutations, demonstrating their essential role for normal brain function. The cryo-EM structure of a hetero-tetramer in the apo state reveals the heterodimers interacting in an asymmetrical way to prevent one unit from being activated. This represents a nice example of a negative allosteric interaction between GPCRs related to human diseases.