関連する実験動画
Updated: Jul 2, 2026

06:06
In Vitro Analysis of E3 Ubiquitin Ligase Function
Published on: May 14, 2021
Lys 63 リンクされたポリユビキチン鎖の特定の割れ目の構造的基礎
Yusuke Sato1, Azusa Yoshikawa, Atsushi Yamagata
1Structural Biology Laboratory, Life Science Division, Synchrotron Radiation Research Organization and Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.
Nature
|September 2, 2008
まとめ
この研究は,特定のユビキチン鎖と複合したデウビキチン化酵素 (DUB) であるAMSH-LPの構造を明らかにした. この構造は,AMSH-LPが,受容体密輸に不可欠な,Lys 63結合ポリユビキチン鎖をどのように除去するのかを明確にします.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 構造生物学 構造生物学とは
背景:
- 脱ユビキチン化酵素 (DUB) は,ユビキチンを除去することによって,細胞過程の重要な調節因子です.
- AMSHとAMSH-LPは,リンチに依存するDUBであり,Lys 63結合型ポリユビキチン鎖の分裂経由で受容体取引に関与しています.
研究 の 目的:
- 人間のAMSH-LP DUB領域の結晶構造を決定するために.
- AMSHファミリーのメンバーによるLys 63結合固有のデウビキチン化のメカニズムを解明する.
主な方法:
- X線結晶学を用いて,AMSH-LP DUBドメインの構造を単独で,およびLys 63結合ダイユビキチンとの複合体で得られた.
- 高解像度構造分析 (1.2Aと1.6A) を実施した.
主要な成果:
- AMSH-LP DUBドメインの結晶構造は,2つの挿入 (Ins-1とIns-2) を有する触媒コアを示しています.
- 構造は,酵素と Lys 63 結合鎖の遠端および近端のユビキチン分子の間の特定の相互作用を示しています.
- 重要なユビキチン残留物とイソペプチド結合を収納する触媒槽が特定されました.
結論:
- これは,イソペプチド結合ユビキチン鎖と複合したDUBの構造が初めて報告されたものです.
- この発見は,AMSHファミリーDUBによるLys 63結合特異デウビキチン化の原因となる分子メカニズムを明らかにしています.
関連する概念動画
The Proteasome
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 (ubiquitin...
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 (ubiquitin...
The Proteasome
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...
Regulated Protein Degradation
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...
Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
The Proteasome Structure
The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...
The proteasome is an...
Protein Complexes with Interchangeable Parts
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...

