分泌前体聚酸与转位子复合物的结合是由BiP调节的
1Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley 94720, USA.
Cell
|January 10, 1997
概括
Sec62p,Sec71p和Sec72p形成一个复合体,将分泌蛋白与ER膜结合起来. 由BiP和Sec63p释放的ATP依赖性释放对于早期ER转移至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 贩卖蛋白质 贩卖蛋白质 是一个问题.
背景情况:
- 通过内质网膜 (ER) 进行分泌蛋白转移对于细胞功能至关重要.
- 这一过程涉及前体蛋白对接,插入和通过蛋白质导电通道 (转位孔) 进行转位.
- 调节前体的初始接触和释放的精确机制仍然不完全理解.
研究的目的:
- 识别和表征涉及到在ER膜上分泌前体的初始参与的蛋白质复合体.
- 阐明特定蛋白质的作用,包括Sec62p,Sec71p,Sec72p,BiP和Sec63p,在ER转位的早期阶段.
- 定义管理前体结合和释放的监管机制.
主要方法:
- 生物化学测试用于研究蛋白质与蛋白质相互作用.
- 在体外复制转位步骤.
- 在不同的ATP条件下分析蛋白质结合和释放动力学.
- 基因操纵以评估关键蛋白质的功能.
主要成果:
- Sec62p,Sec71p和Sec72p形成一个独特的转位子复合体,在ER膜上结合分泌前体.
- 前体结合依赖于完整的信号序列,并且在没有ATP的情况下发生.
- 从这个亚复合体中释放前体的ATP介导释放由光线伴侣BiP及其与Sec63p的相互作用促进.
- 这种BiP-Sec63p介导的释放是特定的,并且发生在转位过程的早期.
结论:
- 该Sec62p-Sec71p-Sec72p复合体作为ER膜上的分泌前体的初始对接点.
- BiP和Sec63p在调节从膜结合复合体中早期释放前体方面发挥着关键作用,促进随后的转位.
- 这些发现揭示了一种新的调节机制,该机制控制了蛋白质转移到ER光层的启动.
相关概念视频
Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
Directing Proteins to the Rough Endoplasmic Reticulum
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
Cotranslational Protein Translocation
Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Post-translational Translocation of Proteins to the RER
A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Protein Translocation Machinery on the ER Membrane
The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the translocon complex.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the translocon complex.
Bacterial Translocation and Protein Secretion
Bacterial protein secretion involves translocation systems to ensure proteins reach their designated locations, including the plasma membrane, periplasm, outer membrane, or the external environment. These translocation systems are vital for bacterial physiology, supporting processes like membrane assembly, enzymatic activity in the periplasm, and interactions with the external environment. The division of labor between Sec and Tat pathways ensures efficiency in handling proteins with diverse...


