Gq-合粘附受体ADGRL4的结构
Qingchao Chen1, Anastasiia Gusach1, Aurora Diamante2
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK.
Nature communications
|December 30, 2025
概括
像ADGRL4一样,粘附G蛋白结合受体 (aGPCRs) 在癌症中至关重要. 这项研究揭示了ADGRL4对Gq蛋白的弱结合,为难治癌症提供了新的治疗点.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 粘附G蛋白结合受体 (aGPCRs) 对包括癌症生物学在内的各种细胞功能至关重要.
- ADGRL4在瘤中升级调节,并与病变发生有关,对质母细胞瘤等癌症具有潜在的治疗点.
研究的目的:
- 为了研究ADGRL4.4的G蛋白合和结构.
- 了解ADGRL4对潜在的癌症治疗的信号传递机制.
主要方法:
- 敏感的生物发光测定检测G蛋白合.
- 低温电子显微镜 (cryo-EM) 用于确定ADGRL4-Gq复合物的结构.
主要成果:
- ADGRL4与Gq蛋白的合较弱,与其他G蛋白或β-arrestin没有显著的合.
- 3.1 Å的冷-EM结构显示ADGRL4的折叠与其他aGPCRs相似,但与Gq.
- 该结构支持ADGRL4由其绑定的激动剂激活.
结论:
- ADGRL4的弱Gq合是一种新发现,对其在癌症中的功能有影响.
- 确定的结构为开发针对各种瘤类型的ADGRL4的向抑制剂提供了基础.
更多相关视频
08:15Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules
Published on: October 17, 2014
10.9K
14:02Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells
Published on: April 9, 2018
9.0K
相关概念视频
Transducer Mechanism: G Protein–Coupled Receptors
3.9K
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
GPCRs are also called heptahelical,...
3.9K
G Protein-coupled Receptors
16.3K
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
16.3K
G-protein Coupled Receptors
131.3K
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
131.3K
Intracellular Signaling Affects Focal Adhesions
3.4K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
3.4K
Assembly of Signaling Complexes
6.4K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
6.4K
Activation and Inactivation of G Proteins
10.7K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
10.7K
