期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 50, 页码 E11751-E11760出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1811580115
关键词
murine leukemia virus; retrovirus; cryoelectron tomography; capsid; maturation
资金
- Deutsche Forschungsgemeinschaft [BR 3635/2-1, KR 906/71, KR 906/8-1]
- EMBL
- European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme [ERC-CoG-648432 MEMBRANEFUSION]
- Medical Research Council [MC_UP_1201/16]
- Czech Science Foundation (GACR) [17-25602S]
- Ministry of Education of the Czech Republic [NPU: LO1302, LO1304, LO1601]
- Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research
- EMBL IT services unit
- EMBL Heidelberg Crystallization Platform
- NATIONAL CANCER INSTITUTE [ZIABC010511] Funding Source: NIH RePORTER
- MRC [MC_UP_1201/16] Funding Source: UKRI
Retroviruses assemble and bud from infected cells in an immature form and require proteolytic maturation for infectivity. The CA (capsid) domains of the Gag polyproteins assemble a protein lattice as a truncated sphere in the immature virion. Proteolytic cleavage of Gag induces dramatic structural rearrangements; a subset of cleaved CA subsequently assembles into the mature core, whose architecture varies among retroviruses. Murine leukemia virus (MLV) is the prototypical gamma-retrovirus and serves as the basis of retroviral vectors, but the structure of the MLV CA layer is unknown. Here we have combined X-ray crystallography with cryoelectron tomography to determine the structures of immature and mature MLV CA layers within authentic viral particles. This reveals the structural changes associated with maturation, and, by comparison with HIV-1, uncovers conserved and variable features. In contrast to HIV-1, most MLV CA is used for assembly of the mature core, which adopts variable, multilayered morphologies and does not form a closed structure. Unlike in HIV-1, there is similarity between protein-protein interfaces in the immature MLV CA layer and those in the mature CA layer, and structural maturation of MLV could be achieved through domain rotations that largely maintain hexameric interactions. Nevertheless, the dramatic architectural change on maturation indicates that extensive disassembly and reassembly are required for mature core growth. The core morphology suggests that wrapping of the genome in CA sheets may be sufficient to protect the MLV ribonucleoprotein during cell entry.
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