流感病毒A M2蛋白产生负高斯膜曲率,这是芽和分裂所必需的
Nathan W Schmidt1, Abhijit Mishra, Jun Wang
1Department of Bioengineering, University of California, Los Angeles , Los Angeles, California 90095, United States.
Journal of the American Chemical Society
|August 22, 2013
概括
流感A病毒的M2蛋白通过重组细胞膜驱动病毒芽. 这种蛋白质产生负高斯曲率 (NGC),对病毒释放至关重要,也是抗病毒疗法的潜在目标.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 生物物理学的生物物理.
背景情况:
- M2蛋白对于流感A病毒的复制至关重要,特别是在成熟的病毒芽过程中.
- 了解M2蛋白在膜动态中的作用是开发新抗病毒策略的关键.
研究的目的:
- 研究M2蛋白质促进流感A病毒芽的机制.
- 确定M2蛋白与脂质膜相互作用的结构基础及其在产生膜曲率中的作用.
主要方法:
- 使用高分辨率小角度X射线散射 (SAXS) 分析M2蛋白对脂质膜的影响.
- 使用野生型M2蛋白和各种突变结构进行了实验,以评估特定域的功能.
主要成果:
- M2蛋白质将脂质膜重组为具有高负高斯曲率 (NGC) 的双连续立方相.
- M2的细胞质两螺旋是NGC生成所必需和足够的,对于病毒芽至关重要.
- M2产生高曲率的能力可与芽病毒的分裂子相提并论,其他域可能会协同增强这种能力.
结论:
- M2诱导的负高斯曲率对于流感病毒的芽至关重要.
- 针对M2的膜曲率生成能力,为开发抗流感疗法提供了一个有前途的战略.
相关概念视频
Leaky Scanning
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 stands for...
Influenza
Influenza is an acute, highly communicable viral disease that affects the respiratory tract and is responsible for seasonal epidemics worldwide. Influenza A is the most prevalent type associated with widespread outbreaks and is subtyped based on two surface glycoproteins: hemagglutinin (H) and neuraminidase (N), as in H1N1. These glycoproteins are essential for viral infectivity, transmission, and immune recognition. Transmission occurs primarily through respiratory droplets and contaminated...
Intracellular Movement of Viruses and Bacteria
Intracellular bacteria and viruses often comprise a group of highly infectious pathogens that can cause several diseases. Bacterial pathogens include those belonging to the genus Rickettsia responsible for conditions such as rocky mountain spotted fever and the Mediterranean spotted fever; Chlamydia, a genus responsible for a sexually transmitted disease; Coxiella burnetii, an agent responsible for Q fever. Viral pathogens include vaccinia—a poxvirus, and herpes simplex virus—a virus that...
Pinching-off of Coated Vesicles
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...
SNAREs and Membrane Fusion
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...
Mechanisms of Membrane-bending
The living membranes are flexible due to their fluid mosaic nature; however, their bending into different shapes is an active process regulated by specific lipids and proteins. The membrane bending can be transient as seen in vesicles or stable for a long time as in microvilli. Cells regulate the size, location, and duration of the membrane curvature.
Membrane bending can happen due to intrinsic changes in lipid composition or extrinsic association with different proteins. The proteins involved...
Membrane bending can happen due to intrinsic changes in lipid composition or extrinsic association with different proteins. The proteins involved...


