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Structure and architecture of immature and mature murine leukemia virus capsids
K. Qu, B. Glass, M. Doležal, FKM. Schur, B. Murciano, A. Rein, M. Rumlová, T. Ruml, HG. Kräusslich, JAG. Briggs,
Language English Country United States
Document type Comparative Study, Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't
NLK
Free Medical Journals
from 1915 to 6 months ago
Freely Accessible Science Journals
from 1915 to 6 months ago
PubMed Central
from 1915 to 6 months ago
Europe PubMed Central
from 1915 to 6 months ago
Open Access Digital Library
from 1915-01-15
Open Access Digital Library
from 1915-01-01
- MeSH
- Cryoelectron Microscopy MeSH
- Gene Products, gag chemistry genetics ultrastructure MeSH
- HEK293 Cells MeSH
- HIV-1 chemistry genetics ultrastructure MeSH
- Capsid chemistry ultrastructure MeSH
- Crystallography, X-Ray MeSH
- Protein Structure, Quaternary MeSH
- Humans MeSH
- Models, Molecular MeSH
- Mice MeSH
- Protein Domains MeSH
- Amino Acid Sequence MeSH
- Sequence Homology, Amino Acid MeSH
- Electron Microscope Tomography MeSH
- Virion chemistry genetics ultrastructure MeSH
- Capsid Proteins chemistry genetics ultrastructure MeSH
- Leukemia Virus, Murine chemistry genetics ultrastructure MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Intramural MeSH
- Comparative Study MeSH
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 γ-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.
Department of Biotechnology University of Chemistry and Technology 16628 Prague 6 Czech Republic
Department of Infectious Diseases Virology Universitätsklinikum Heidelberg 69120 Heidelberg Germany
References provided by Crossref.org
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