The HIV capsid mimics karyopherin engagement of FG-nucleoporins
成果类型：
Article
署名作者：
Dickson, C. F.; Hertel, S.; Tuckwell, A. J.; Li, N.; Ruan, J.; Al-Izzi, S. C.; Ariotti, N.; Sierecki, E.; Gambin, Y.; Morris, R. G.; Towers, G. J.; Bocking, T.; Jacques, D. A.
署名单位：
University of New South Wales Sydney; University of New South Wales Sydney; University of New South Wales Sydney; University of New South Wales Sydney; University of Queensland; University of London; University College London
刊物名称：
Nature
ISSN/ISSBN：
0028-6311
DOI：
10.1038/s41586-023-06969-7
发表日期：
2024-02-22
关键词：
structural basis
nuclear import
binding
sites
beta
Visualization
replication
transport
DYNAMICS
repeats
摘要：
HIV can infect non-dividing cells because the viral capsid can overcome the selective barrier of the nuclear pore complex and deliver the genome directly into the nucleus1,2. Remarkably, the intact HIV capsid is more than 1,000 times larger than the size limit prescribed by the diffusion barrier of the nuclear pore3. This barrier in the central channel of the nuclear pore is composed of intrinsically disordered nucleoporin domains enriched in phenylalanine-glycine (FG) dipeptides. Through multivalent FG interactions, cellular karyopherins and their bound cargoes solubilize in this phase to drive nucleocytoplasmic transport4. By performing an in vitro dissection of the nuclear pore complex, we show that a pocket on the surface of the HIV capsid similarly interacts with FG motifs from multiple nucleoporins and that this interaction licences capsids to penetrate FG-nucleoporin condensates. This karyopherin mimicry model addresses a key conceptual challenge for the role of the HIV capsid in nuclear entry and offers an explanation as to how an exogenous entity much larger than any known cellular cargo may be able to non-destructively breach the nuclear envelope. Dissection of the nuclear pore complex provides a model in which the HIV capsid enters the nucleus through karyopherin mimicry, a mechanism likely to be conserved across other viruses.