动态的多体蛋白相互作用表明铜走私的多功能途径
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
概括
人类的铜伴侣Hah1将铜送给威尔逊.
科学领域:
- 生物化学和分子生物学
- 细胞内铜运输机制
背景情况:
- 人类的铜伴侣Hah1促进细胞内铜 (Cu+) 输送到威尔逊病蛋白 (WDP).
- WDP拥有六个金属结合域 (MBD),这些域从Hah1接收Cu+,但多个MBD在铜贩运中的作用尚不清楚.
- 之前的研究探讨了Hah1与孤立的WDP MBDs的相互作用.
研究的目的:
- 为了研究Hah1与双域WDP结构 (MBD34) 之间的相互作用动态.
- 了解Hah1如何与WDP多域系统中的多个MBD相互作用.
- 阐明MBD多重性在铜贩运中的功能意义.
主要方法:
- 使用单分子光共振能量转移 (smFRET) 结合囊泡捕获.
- 系统地探测了Hah1-MBD3,Hah1-MBD4和分子内MBD3-MBD4的相互作用动态.
- 利用交替的捐赠者和接受者位置来分析相互作用几何.
主要成果:
- 在分子间Hah1-MBD和分子内MBD-MBD相互作用中观察到保守的相互转换相互作用几何.
- 发现MBD34结构中的Hah1-MBD相互作用与孤立的单个MBD相比稳定了数量级.
- 收集的热力学和动力学证据表明,Hah1可以与MBD3和MBD4同时相互作用.
结论:
- 增强的Hah1与多MBD系统的相互作用稳定性表明一个更强大的铜输送机制.
- 动态的分子内MBD-MBD相互作用有助于铜贩运的多功能性.
- 由于Hah1能够与多个WDP MBD同时交互,这表明Hah1到WDP的铜运输途径是高效且可适应的.
更多相关视频
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
相关概念视频
Protein 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,...
Assembly 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,...
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...
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...
Cooperative 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...
Overview 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...
