复杂形式受限的共价TRMT112连接体,可在异质上对METTL5产生痛苦.
F Wieland Goetzke1, Steffen M Bernard2, Cheng-Wei Ju3,4,5
1Department of Chemistry, Scripps Research, La Jolla, CA, USA. fgoetzke@scripps.edu.
Nature chemical biology
|January 8, 2026
概括
研究人员开发了化学探针,专门针对TRMT112适配蛋白,当它与METTL5.5相互作用时. 这种方法可以实现特定对象的功能效应,克服研究可适应蛋白质的挑战.
科学领域:
- 化学生物学 化学生物学
- 分子细胞生物学 分子细胞生物学
- 蛋白质生物化学 蛋白质生物化学
背景情况:
- 适应蛋白调节多个蛋白质复合体,使其研究复杂化,因为在遗传中断时具有类效应.
- TRMT112是一种甲基转移酶 (MT) 适配器,通过不同的复杂形式参与各种细胞功能.
研究的目的:
- 开发化学蛋白质学工具,用于研究适应蛋白质复杂形式.
- 研究TRMT112与甲基转移酶 (MTs) 的特定相互作用.
主要方法:
- 双cyclopyrrolidine烯胺的化学蛋白质的发现立体检测.
- 评估与重组TRMT112及其复合物与MTs的立体探针反应性.
- 结晶学用于确定立体探测器的结合模式.
主要成果:
- 在METTL5的存在下,立体探测器选择性地与TRMT112反应,但与未复合的TRMT112或其他TRMT112:MT复合物没有反应.
- 晶结构揭示了一个由METTL5.5模板的复合粘合口袋.
- 立体检测试剂的结合诱导了METTL5活性的全激应.
结论:
- 共价联体可以通过准独特的适应器复杂形状来实现对象特异性的功能效应.
- 这项研究提供了一种新的化学生物学方法,以复杂型特异的方式剖析适应蛋白功能.
相关概念视频
Cooperative Allosteric Transitions
8.6K
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...
8.6K
Cooperative Allosteric Transitions
2.6K
2.6K
Cooperative Allosteric Transitions
3.0K
3.0K
Metal-Ligand Bonds
23.9K
The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
23.9K
Complexometric Titration: Ligands
2.2K
Different monodentate and polydentate ligands are used as complexing agents in complexometric titration reactions. The formation of complexes by mono- and bidentate ligands involves two or more intermediate steps, limiting their use as complexing agents. In comparison, polydentate ligands can form complexes with metal ions in a single-step process, facilitating sharper end points. This means polydentate ligands, such as amino carboxylic acid derivatives, are most commonly employed in...
2.2K
Complexation Equilibria: The Chelate Effect
1.2K
In complexation reactions, metal atoms or cations interact with ligands to form donor-acceptor adducts called metal complexes. Ligands that bind through one donor site are monodentate, ligands with two donor sites are bidentate, and those with more than two donor sites are polydentate ligands. For example, ethylene diamine is a bidentate ligand that binds through two nitrogen donor atoms, forming a five-membered ring. EDTA is a polydentate ligand that binds through four oxygen and two nitrogen...
1.2K


