ダイナミックな多体タンパク質の相互作用は,銅の密輸のための汎用的な経路を示唆しています
Aaron M Keller1, Jaime J Benítez, Derek Klarin
1Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.
Journal of the American Chemical Society
|May 15, 2012
まとめ
銅を運ぶ人間ハハ1が,ウィルソンに銅を運ぶ.
科学分野:
- バイオケミストリーと分子生物学
- 細胞内銅輸送メカニズム
背景:
- 人間の銅チャペロンであるHah1は,ウィルソン病タンパク質 (WDP) への細胞内銅 (Cu+) 伝達を促進する.
- WDPは,Hah1からCu+を受け取る6つの金属結合ドメイン (MBD) を保有しているが,銅の密輸における複数のMBDの役割は不明である.
- 以前の研究では,孤立したWDP MBDsとのHah1相互作用が調査されました.
研究 の 目的:
- Hah1 とダブルドメイン WDP コンストクト (MBD34) の間の相互作用ダイナミクスを調査する.
- WDP多領域システム内の複数のMBDとHah1がどのように相互作用するかを理解する.
- 銅の密輸におけるMBDの多様性の機能的重要性を明らかにする.
主な方法:
- 単一分子光共振エネルギー伝送 (smFRET) を使用し,膀トラッピングと組み合わせた.
- Hah1-MBD3,Hah1-MBD4,および分子内MBD3-MBD4の相互作用ダイナミクスを体系的に探査しました.
- 相互作用の幾何学を分析するために,ドナーと受容体の位置を交互に利用した.
主要な成果:
- 観察された相互変換相互作用の幾何学は,分子間Hah1-MBDと分子内MBD-MBDの相互作用の両方で保存されています.
- MBD34コンストラクット内のHah1-MBDの相互作用は,単一のMBDと比較して,大きさの順序で安定していることが判明しました.
- 集めた熱力学および運動学的証拠は,Hah1が同時にMBD3とMBD4の両方と相互作用することを示しています.
結論:
- Hah1のマルチMBDシステムとの強化された相互作用安定性は,より堅牢な銅配送メカニズムを示唆しています.
- ダイナミックな分子内MBD-MBDの相互作用は,銅の密輸の多様性に寄与する.
- Hah1が複数のWDP MBDと同時に相互作用する能力は,Hah1からWDPへの銅輸送経路が効率的で適応可能であることを示しています.
さらに関連する動画
11:04Ion Mobility-Mass Spectrometry Techniques for Determining the Structure and Mechanisms of Metal Ion Recognition and Redox Activity of Metal Binding Oligopeptides
Published on: September 7, 2019
11:38Quantifying the Binding Interactions Between Cu(II) and Peptide Residues in the Presence and Absence of Chromophores
Published on: April 5, 2022
関連する概念動画
02:26Protein Networks
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
01:30Assembly of Signaling Complexes
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,...
01:57Protein 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...
01:57Protein 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...
01:58Cooperative Allosteric Transitions
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
01:45Overview of Protein Sorting and Transport
Eukaryotic cells have different membrane-bound organelles with distinct protein requirements. The process by which proteins are targeted to a specific organelle is called protein sorting.
Protein sorting can be of two types: signal-based sorting and vesicle-based trafficking. In signal-based sorting, specific amino acid sequences called sorting signals target proteins to the proper location inside the cell either via gated transport or by protein translocation. In gated transport, folded...
Protein sorting can be of two types: signal-based sorting and vesicle-based trafficking. In signal-based sorting, specific amino acid sequences called sorting signals target proteins to the proper location inside the cell either via gated transport or by protein translocation. In gated transport, folded...