相关实验视频

Updated: Jul 4, 2025

Expression, Solubilization, and Purification of Eukaryotic Borate Transporters

Expression, Solubilization, and Purification of Eukaryotic Borate Transporters

Published on: March 7, 2019

对细菌ClpP功能的动态调节和由二胺化合物进行的寡合化的分子见解

Bruno Alves França¹, Sven Falke², Holger Rohde³

¹Institute of Biochemistry and Molecular Biology, Laboratory for Structural Biology of Infection and Inflammation, University of Hamburg, c/o DESY, Build. 22a, Notkestraße 85, 22607, Hamburg, Germany.

Scientific reports

|January 31, 2024

概括

细菌的代蛋白酶P (ClpP) 结构揭示了ixazomib如何悖论地激活它. 这项研究解释了酶.

科学领域:

生物化学生物化学
结构生物学结构生物学
微生物学微生物学

背景情况:

细菌病原分解蛋白酶P (ClpP) 对于细菌的生存和传染性至关重要.
已知ClpP的复杂结构-功能关系及其14个催化位点,但其通过二甲基酸盐的全调节仍然不清楚.
这些化合物矛盾地刺激了ClpP的活性,而不是抑制它.

研究的目的:

为了阐明通过型酸盐对细菌ClpP的悖论性性激活.
确定Staphylococcus epidermidis ClpP (SeClpP) 的晶体结构及其与ixazomib的复合物.
为了研究由ixazomib引起的形状变化和组装状态.

主要方法:

原生SeClpP和SeClpP-ixazomib复合物的X射线晶体学 (1.90 Å和2.33 Å分辨率).
生物化学和生物物理分析.
使用小角度X射线散射 (SEC-SAXS) 和动态光散射 (DLS) 测量的大小排除色谱.

主要成果:

晶体结构揭示了ixazomib如何与SeClpP相互作用,影响其结构状态和活性.
生物化学和生物物理数据支持结构发现.
首次证明,二甲基酸盐可以诱导阳性生物体中从heptameric环中产生的ClpP的四度组合.

结论:

伊克萨佐米布与SeClpP的结合解释了矛盾的激活机制.
这项研究提供了关于酸盐对ClpP全调节的结构性见解.
这项工作为开发针对ClpP的新型抗菌策略提供了基础.

更多相关视频

X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050

X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050

Published on: May 13, 2020

Analyzing Dynamic Protein Complexes Assembled On and Released From Biolayer Interferometry Biosensor Using Mass Spectrometry and Electron Microscopy

Analyzing Dynamic Protein Complexes Assembled On and Released From Biolayer Interferometry Biosensor Using Mass Spectrometry and Electron Microscopy

Published on: August 6, 2018

相关概念视频

Pinching-off of Coated Vesicles

Pinching-off of Coated Vesicles

Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...

Covalently Linked Protein Regulators

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....

Cooperative Allosteric Transitions

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...