一种膜蛋白,它是 ER 中错误折叠的蛋白质脱离位置所必需的
Brendan N Lilley1, Hidde L Ploegh
1Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature
|June 25, 2004
概括
细胞内膜网 (ER) 中错误折叠的蛋白质被降解. 人类细胞巨型病毒US11糖蛋白为Derlin-1招募蛋白质,这是从ER中提取错误折叠的蛋白质必不可少的因素.
科学领域:
- 细胞生物学 细胞生物学
- 病毒学 病毒学
- 蛋白质降解 蛋白质降解
背景情况:
- 蛋白质错误折叠在内分泌网膜 (ER) 中是降解的目标.
- 这一过程涉及到细胞质溶液的脱位,随后是无处不在化,脱糖化和蛋白质体降解.
- 调解ER蛋白提取的机制在很大程度上仍然没有被描述.
研究的目的:
- 研究人类细胞巨乳病毒 (CMV) 糖蛋白US2和US11调解宿主蛋白质降解的机制.
- 为了确定细胞因子涉及错误折叠的蛋白质从ER的脱.
主要方法:
- 研究了人类细胞巨乳病毒 (CMV) 糖蛋白US2和US11在蛋白质降解中的作用.
- 研究了US11与细胞蛋白的相互作用,使用其跨膜域.
- 评估了Derlin-1的功能,这是酵母Der1p的人类同类物,在I类主要基因相容性复合体 (MHC) 分子的降解中.
主要成果:
- 人类CMV US11糖蛋白招募I类MHC产品到德林-1.
- 德林-1对于US11介导的I类MHC分子的降解至关重要.
- 对于US2介导的I类MHC分子降解,Derlin-1不需要.
结论:
- 德林-1在从哺乳动物ER中提取特定的错误折叠蛋白质方面发挥着至关重要的作用.
- 这突出了Derlin-1作为某些基质的ER相关降解 (ERAD) 途径的关键组成部分.
相关概念视频
01:45ER Retrieval Pathway
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...
01:43The Endoplasmic Reticulum
The endoplasmic reticulum or ER makes up for more than half of the membranes in a cell and accounts for 10% of total cell volume. It is also the primary protein and lipid synthesis factory for most cell organelles, such as the Golgi apparatus, lysosomes, secretory vesicles, and the plasma membrane. Despite being the most extensive and functionally complex subcellular organelle, ER was the last to be discovered. After years of deliberation, Keith Porter and George Palade in the year 1954,...
01:26Insertion of Single-pass Transmembrane Proteins in the RER
Integral membrane proteins are proteins adhered to the lipid bilayer of a cell organelle or membrane. They can be of two types: transmembrane integral proteins that span the lipid bilayer and monotopic proteins that are attached to either side of the membrane but do not pass through it.
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
01:29Protein Folding Quality Check in the RER
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
01:28Assembly of the Lipid Bilayer in the ER
Biological membranes are more than just a barrier separating cell cytoplasm from the outside environment. They are highly dynamic and help maintain the integrity and physiological stability of the cells as well as membrane-bound organelles. Membranes also play vital roles in cell-to-cell and intracellular communication.
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...
01:43The Endoplasmic Reticulum
The endoplasmic reticulum or ER makes up for more than half of the membranes in a cell and accounts for 10% of total cell volume. It is also the primary protein and lipid synthesis factory for most cell organelles, such as the Golgi apparatus, lysosomes, secretory vesicles, and the plasma membrane. Despite being the most extensive and functionally complex subcellular organelle, ER was the last to be discovered. After years of deliberation, Keith Porter and George Palade in the year 1954,...