期刊
NATURE
卷 536, 期 7616, 页码 349-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature19098
关键词
-
资金
- Medical Research Council (UK) [U105181010]
- European Research Council [281627 -IAI]
- European Research Council under the European Union
- ERC [339223]
- National Institute for Health Research University College London Hospitals Biomedical Research Centre
- Wellcome Trust
- NHMRC [GNT1036521]
- Emmanuel College, Cambridge
- European Research Council (ERC) [339223] Funding Source: European Research Council (ERC)
- Medical Research Council [MC_PC_12024, MC_U105181010, 1368839] Funding Source: researchfish
- MRC [MC_U105181010, G9721629, G0801172, MC_PC_12024] Funding Source: UKRI
During the early stages of infection, the HIV-1 capsid protects viral components from cytosolic sensors and nucleases such as cGAS and TREX, respectively, while allowing access to nucleotides for efficient reverse transcription1. Here we show that each capsid hexamer has a size-selective pore bound by a ring of six arginine residues and a 'molecular iris' formed by the amino-terminal beta-hairpin. The arginine ring creates a strongly positively charged channel that recruits the four nucleotides with on-rates that approach diffusion limits. Progressive removal of pore arginines results in a dose-dependent and concomitant decrease in nucleotide affinity, reverse transcription and infectivity. This positively charged channel is universally conserved in lentiviral capsids despite the fact that it is strongly destabilizing without nucleotides to counteract charge repulsion. We also describe a channel inhibitor, hexacarboxybenzene, which competes for nucleotide binding and efficiently blocks encapsidated reverse transcription, demonstrating the tractability of the pore as a novel drug target.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据