CRYOELECTRON MICROSCOPY REVEALS ORDERED DOMAINS IN THE IMMATURE HIV-1PARTICLE

Citation
Sd. Fuller et al., CRYOELECTRON MICROSCOPY REVEALS ORDERED DOMAINS IN THE IMMATURE HIV-1PARTICLE, Current biology, 7(10), 1997, pp. 729-738
Citations number
63
Categorie Soggetti
Biology,Biology
Journal title
ISSN journal
09609822
Volume
7
Issue
10
Year of publication
1997
Pages
729 - 738
Database
ISI
SICI code
0960-9822(1997)7:10<729:CMRODI>2.0.ZU;2-9
Abstract
Background: Human immunodeficiency virus type1 (HIV-1) is the causativ e agent of AIDS and the subject of intense study. The immature HIV-1 p article is traditionally described as having a well ordered, icosahedr al structure made up of uncleaved Gag protein surrounded by a lipid bi layer containing envelope proteins. Expression of the Gag protein in e ukaryotic cells leads to the budding of membranous virus-like particle s (VLPs). Results: We have used cryo-electron microscopy of VLPs from insect cells and lightly fixed, immature HIV-1 particles from human ly mphocytes to determine their organization. Both types of particle were heterogeneous in size, varying in diameter from 1200-2600 Angstrom. L arger particles appeared to be broken into semispherical sectors, each having a radius of curvature of approximately 750 Angstrom. No eviden ce of icosahedral symmetry was found, but local order was evidenced by small arrays of Gag protein that formed facets within the curved sect ors. A consistent 270 Angstrom radial density was seen, which included a 70 Angstrom wide low density feature corresponding to the carboxy-t erminal portion of the membrane attached matrix protein and the amino- terminal portion of the capsid protein. Conclusions: Immature HIV-1 pa rticles and VLPs both have a multi-sector structure characterized, not by an icosahedral organization, but by local order in which the struc tures of the matrix and capsid regions of Gag change upon cleavage. We propose a model in which lateral interactions between Gag protein mol ecules yields arrays that are organized into sectors for budding by RN A. (C) Current Biology Ltd ISSN 0960-9822.