这是头还是尾? 一种分子动力学方法来了解TNF相关因子TRAF2的复杂结构
Fulvio Erba1, Luisa Di Paola2, Almerinda Di Venere3
1Department of Clinical Science and Translational Medicine, Tor Vergata University of Rome, Via Montpellier 1, 00133 Rome, Italy.
Biomolecular concepts
|June 28, 2023
概括
瘤坏死因子受体-关联因子2 (TRAF2) 蛋白质的N端尾的长度显著影响了它们的动态. 更长的尾巴导致更有序的运动,影响蛋白质相互作用和功能.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 计算生物学 计算生物学
背景情况:
- 瘤坏死因子受体相关因子 (TRAF) 蛋白质是关键的信号中间体.
- TRAFs将瘤坏死因子 (TNF) 受体与下游信号通路联系起来.
- TRAF蛋白具有共同的结构:一个C端的球状域和一个N端的卷轴尾巴.
研究的目的:
- 研究N端尾巴长度对TRAF2蛋白质动态的影响.
- 分析尾巴长度如何影响TRAF2.2的四分体结构和单体运动.
- 为了阐明TRAF单体-三元体平衡在体内蛋白质功能中的作用.
主要方法:
- 使用计算方法对TRAF2动态进行了In Silico分析.
- 使用了TRAF2 C端片段 (TRAF2-C) 的晶体结构.
- 使用AlphaFold2.2重建了一个更长的TRAF2结构 (TRAF2-plus).
主要成果:
- TRAF2-plus的延长的N端尾部显著影响其C端球状区域的动态.
- 随着时间的推移,TRAF2-C子单元内的四次相互作用表现出不对称的变化.
- 与较短的TRAF2-C结构相比,TRAF2-plus单体表现出更有限和有序的运动.
结论:
- 尾巴的N端长度是TRAF2子单元动态的一个关键决定因素.
- 由于尾巴长度而改变的动力学影响蛋白质相互作用和四级结构.
- 这些发现提供了对TRAF蛋白机制的洞察,包括体内受体识别和寡合化.
更多相关视频
10:41Conjugative Mating Assays for Sequence-specific Analysis of Transfer Proteins Involved in Bacterial Conjugation
Published on: January 4, 2017
13.9K
16:10A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins
Published on: March 22, 2012
23.9K
相关概念视频
TGF - β Signaling Pathway
7.5K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.5K
Intracellular Signaling Affects Focal Adhesions
2.7K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.7K
Assembly of Signaling Complexes
5.8K
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,...
5.8K
MAPK Signaling Cascades
5.7K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.7K
Tail-anchoring of Proteins in the ER Membrane
3.1K
Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
3.1K
