一个不成熟的人体内源性逆转录病毒的分子结构和保护
Anna-Sophia Krebs1, Hsuan-Fu Liu2, Ye Zhou3
1Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Nature communications
|August 24, 2023
概括
未成熟的人体内源性逆转录病毒K (HERV-K) 囊体结构显示了保存的组装和成熟机制. 这一发现提供了对逆转录病毒演变和癌症和ALS的潜在治疗点的见解.
科学领域:
- 结构生物学 结构生物学
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 人体内源逆转录病毒K (HERV-K) 是人类基因组中最近获得的内源逆转录病毒.
- HERV-K在各种癌症和肌缩性侧面硬化症 (ALS) 中被激活和表达.
研究的目的:
- 在高分辨率下确定未成熟的HERV-K体结构.
- 为了阐明HERV-K体的组装和成熟机制.
主要方法:
- 用冷电子断层扫描和亚断层扫描平均值来确定来自本地病毒样颗粒的结构.
- 用全原子分子动力学模拟和突变研究来分析组装接口和构造变化.
主要成果:
- 未成熟的HERV-K体结构在3.2 Å分辨率下得到了分辨.
- 一个六合体单元,通过一个由IP6相似分子稳定的6螺旋捆绑 oligomerized,形成状网格.
- 高度保存的二元和三元接口介于组装,在成熟过程中发生了很大的形状变化.
结论:
- HERV-K囊组装和成熟与其他逆转录病毒共享保护机制,跨越基因和进化时间.
- 这些发现提供了对HERV-K的结构洞察力,HERV-K是一种涉及癌症和ALS等疾病的病毒.
相关概念视频
Retroviruses
12.4K
Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
12.4K
Retrovirus Life Cycles
46.2K
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
46.2K
Size and Structure of Viral Genomes
59
Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
59
LTR Retrotransposons
17.6K
LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
17.6K
Non-LTR Retrotransposons
11.6K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
11.6K
Mechanisms of Retrovirus-induced Cancers
5.1K
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
5.1K


