GABARAP与EGFR相互作用 - 支持该hAtg8蛋白在受体贩运过程中的独特作用
Alina Üffing1,2, Oliver H Weiergräber1,2, Melanie Schwarten2
1Heinrich-Heine-Universität Düsseldorf, Mathematisch-Naturwissenschaftliche Fakultät, Institut für Physikalische Biologie, Düsseldorf, Germany.
FEBS letters
|August 19, 2024
概括
自蛋白GABARAP直接与表皮生长因子受体 (EGFR) 结合. 这种相互作用影响EGFR降解,突出了GABARAP在受体调节中的新角色.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 人类GABARAP蛋白,Atg8家族的一部分,参与各种细胞过程,包括自.
- 之前已经观察到,GABARAP缺乏会在带刺激后增强表皮生长因子受体 (EGFR) 降解.
研究的目的:
- 调查GABARAP和EGFR之间的直接相互作用.
- 确定参与这种相互作用的特定地区,并阐明约束机制.
主要方法:
- 在分析中预测EGFR上的GABARAP结合点.
- 在体外结合测定以确认GABARAP-EGFR相互作用.
- 进行X射线晶体学以确定结合物的结构基础.
主要成果:
- 在EGFR中确定了两个潜在的LC3相互作用区域 (LIR);LIR1被预测并确认为GABARAP结合部位.
- 在体外,EGFR LIR1优先与GABARAP和GABARAPL1结合.
- X射线结晶学揭示了LIR1残留物和GABARAP的疏水口袋之间的正规结合模式.
结论:
- 格巴拉普通过其LIR1区域直接与EGFR结合.
- 这种直接相互作用是GABARAP影响EGFR降解和细胞命运的关键机制.
相关概念视频
Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K
Assembly of Signaling Complexes
5.7K
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,...
5.7K
Enzyme-linked Receptors
77.7K
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
77.7K
Mitogens and the Cell Cycle
6.4K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.4K
ER Retrieval Pathway
3.8K
In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
3.8K
Rab Proteins
3.9K
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
3.9K


