核进口乙型肝炎病毒 (HBV) 核囊核核核核的结构基础
Ruoyu Yang1, Ying-Hui Ko2, Fenglin Li1
1Department of Biochemistry and Molecular Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
Science advances
|January 10, 2024
概括
乙型肝炎病毒 (HBV) 囊核进口是复制的关键. 进口因α1识别了体上暴露的核定位信号 (NLS),促进了核孔复合体的转移.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 乙型肝炎病毒 (HBV) 核体的核进口对于宿主细胞核内的病毒复制至关重要.
- 大约直径360安格斯特姆的HBV囊体通过核孔复合体 (NPC) 进入完好无损的核.
- 这个过程涉及劫持宿主进口蛋白质,这是由细胞激酶调节的反应.
研究的目的:
- 阐明HBV囊体被进口蛋白识别的分子机制.
- 为了研究酸化在体-宿主蛋白相互作用和核进口中的作用.
主要方法:
- 对HBV素-进口素相互作用的结构分析.
- 在HBV外衣蛋白 (Cp183) 上核定位信号 (NLS) 的识别和表征.
- 生物化学试验,以评估酸化对NLS暴露和importin结合亲和力的影响.
主要成果:
- 进口因α1直接与位于HBV外衣蛋白Cp183.3的碳基终端域 (CTD) 的特定NLS结合.
- 这种NLS可以通过在近六倍顶点的孔隙在体表面上访问.
- 在CTD中酸化氨酸残留物 (S155,S162,S170) 促进其紧缩,但不会改变importin α1结合亲和力.
- 进口素α1/β1的结合使HBV囊体直径增加到~620司,使其能够通过NPC.
结论:
- 化HBV体CTD可能有助于其外部化和紧缩,使NLS暴露在进口识别中.
- 进口中介的囊体大小的增加是核转移和随后的病毒复制的关键步骤.
相关概念视频
Nuclear Localization Signals and Import
5.7K
Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of 2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
5.7K
Viral Structure
62.3K
Viruses are extraordinarily diverse in shape and size, but they all have several structural features in common. All viruses have a core that contains a DNA- or RNA-based genome. The core is surrounded by a protective coat of proteins called the capsid. The capsid is composed of subunits called capsomeres. The capsid and genome-containing core are together known as the nucleocapsid.
62.3K
Nuclear Protein Sorting
4.6K
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
4.6K
Nuclear Export
3.6K
The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
3.6K
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
The Nucleosome Core Particle
918
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
918


