生体細胞におけるタンパク質の活性を制御するための外因的障害
Onur Dagliyan1,2,3, Miroslaw Tarnawski4, Pei-Hsuan Chu3
1Program in Molecular and Cellular Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Science (New York, N.Y.)
|December 17, 2016
まとめ
科学者は光や化学物質を使って タンパク質の機能を制御するスイッチを設計しました この広く適用可能な方法は 精密にタンパク質の活性と 細胞の行動を調節し 生物学的研究のための新しいツールを提供します
科学分野:
- 生物化学
- 分子生物学
- 細胞生物学
背景:
- オプトジェネティクスとケミオジェネティクスにより タンパク質のシグナルダイナミクスを正確に制御できます
- 調節性タンパク質構造障害は,アロステリック制御に新しいアプローチを提供します.
研究 の 目的:
- アロステルタンパク質スイッチを生成するための広く適用可能な方法を開発する.
- エンジニアリングのスイッチを使って タンパク質の構成と細胞の形態動力学の制御を調査する.
主な方法:
- 表面に露出するタンパク質ループに光やリガンドに敏感なドメインを挿入することによって,設計されたアロステリックスイッチ.
- 活性部位にアロステリックで結合した計算で特定されたタンパク質のループ.
- キナーゼ,グアノシントライフォスファタゼ (GTPases),グアニン交換因子 (GEFs) を含む運動性シグナリングタンパク質にスイッチを導入した.
主要な成果:
- 強力なアロステリックスイッチを作るために 多様なタンパク質の構造的障害をうまく調節した.
- 自然の活性タンパク質と非活性タンパク質の制御された変換を達成した.
- 生体細胞のモルフォダイナミクスを 設計されたタンパク質スイッチで 変調することが示されています
結論:
- このアプローチは,機能的なタンパク質スイッチの設計に多岐にわたる戦略を提供します.
- 設計されたアロステリックスイッチは タンパク質の機能と細胞のプロセスを 精密に制御します
- この方法は生物学的研究と合成生物学において広く適用可能である.
関連する概念動画
02:11Proteins: From Genes to Degradation
14.8K
Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick. Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
Transcription is the synthesis of RNA...
Transcription is the synthesis of RNA...
14.8K
02:58Regulated Protein Degradation
9.1K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
9.1K
01:13The Proteasome
1.9K
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
1.9K
02:18The Proteasome
10.4K
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
10.4K
02:18Intrinsically Disordered Proteins
20.5K
Intrinsically disordered proteins are a group of proteins that do not fold into specific three-dimensional structures. Their structural flexibility allows them to complement ordered proteins to perform functions that are inaccessible to rigid structures. They are more common in eukaryotes than prokaryotes and may either be exclusively intrinsically disordered or hybrid proteins, consisting of a mix of ordered and disordered regions. The absence of a rigid structure in these proteins can be...
20.5K
01:37The Unfolded Protein Response
6.6K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.6K