在膜融合后登革热病毒包膜蛋白的结构
Yorgo Modis1, Steven Ogata, David Clements
1Howard Hughes Medical Institute, Children's Hospital and Harvard Medical School, 320 Longwood Avenue, Boston, Massachusetts 02115, USA.
Nature
|January 23, 2004
概括
登革热病毒使用它的包裹糖蛋白E与宿主细胞融合. 结构分析揭示了融合后的状态,具有促进膜插入的融合环,这表明了新的抗病毒策略.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 登革热病毒通过其外糖蛋白E感染宿主细胞.
- 病毒的进入涉及到由内体pH触发的葡萄糖蛋白E的构造变化.
- 了解这些变化对于开发抗病毒疗法至关重要.
研究的目的:
- 为了确定三维结构的登革热病毒溶性E ectodomain (sE) 在其后融合状态.
- 为了建模病毒与宿主膜融合的机制.
- 为了识别潜在的目标来抑制病毒的进入.
主要方法:
- 进行X射线晶体学以确定三合体的结构,融合后的SE.
- 结构分析和比较与二维,预注射形式.
- 模拟与脂质双层的融合循环相互作用.
主要成果:
- 融合后的SE ectodomain采用了延长的三元体结构,与二维预注的形式不同.
- 三个"融合环"暴露在三分器的一端,用于宿主细胞膜插入.
- 结构显示出"折叠后"的形状,将碳氧末端指向聚变环.
结论:
- 提出了一个由糖蛋白E的不可逆转的构造变化驱动的融合机制.
- 融合循环插入脂质双层是一个关键的步骤,由折叠背结构促进.
- 特定的结构特征为抑制病毒进入提供了潜在的策略.
相关概念视频
Viral Structure
59.0K
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.
59.0K
Leaky Scanning
4.5K
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...
4.5K
Fusion of Secretory Vesicles with the Plasma Membrane
15.9K
Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
15.9K
Pinching-off of Coated Vesicles
3.1K
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...
3.1K
SNAREs and Membrane Fusion
10.4K
Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
10.4K
Introduction to Virus
2.9K
Viruses are unique biological entities that blur the boundary between living and non-living systems. Although they lack cellular structure and metabolic processes, they can exhibit characteristics of life when infecting a host. Their defining feature is a nucleic acid core, composed of either DNA or RNA, encapsulated within a protein coat called a capsid. This simple structure allows them to invade host cells and use their machinery for replication efficiently.Viral Structure and...
2.9K


