双重化和脂质结合的结合平衡调节SARS Cov 2 Orf9b相互作用和干扰素反应
C J San Felipe1, Jyoti Batra2,3,4, Monita Muralidharan2,3,4
1Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158.
bioRxiv : the preprint server for biology
|March 3, 2025
概括
SARS-CoV-2 Orf9b 蛋白质通过结合 Tom70.0.b 抑制先天免疫力. 脂质结合稳定Orf9b二元体,影响其与Tom70的相互作用和感染期间的干扰素信号传递.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 免疫学 免疫学 免疫学
背景情况:
- 开放阅读框架9b (Orf9b) 是一种SARS-CoV和SARS-CoV-2蛋白质,对于抑制天生的免疫力至关重要.
- Orf9b与外膜70 (Tom70) 的线粒体受体转位酶相互作用.
- Orf9b表现出不同的构造:单独的同聚体和与Tom70.0结合时的单聚体.
研究的目的:
- 开发一种生物物理模型来量化Orf9b的结构转换和Tom70结合.
- 为了研究脂质结合和SARS-CoV-2变异对Orf9b:Tom70平衡的影响.
主要方法:
- 生物物理建模分析Orf9b的结构动态.
- Orf9b:Tom70结合动力学和平衡的表征.
- 评估脂质和变异突变对Orf9b行为的影响.
主要成果:
- 一种与Orf9b同分体结合的脂质将平衡转移到二分体状态,通过降低解离速率~100倍.
- 关注SARS-CoV-2变异的突变可以改变特定的速率常数,而不会显著影响Tom70结合.
- 偶联平衡中的扰乱会影响Orf9b对Tom70.0.的明显亲和力.
结论:
- 这项研究为Orf9b的形状变化和Tom70相互作用提供了定量模型.
- 脂质结合和病毒变异调节Orf9b功能,影响先天免疫抑制.
- 这些发现提供了对冠状病毒感染机制和干扰素信号传递的潜在治疗点的见解.
相关概念视频
Conjugated Proteins
18.2K
Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
18.2K
Cooperative Binding of Transcription Regulators
6.3K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
6.3K
Cooperative Allosteric Transitions
7.8K
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...
7.8K
Ligand Binding and Linkage
4.7K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
4.7K
Assembly of Signaling Complexes
5.7K
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,...
5.7K
Leaky Scanning
5.1K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K


