Conserved and variable features of Gag structure and arrangement in immature retrovirus particles.
The assembly of retroviruses is driven by oligomerization of the Gag polyprotein. We have used cryo-electron tomography together with subtomogram averaging to describe the three-dimensional structure of in vitro-assembled Gag particles from human immunodeficiency virus, Mason-Pfizer monkey virus, and Rous sarcoma virus. These represent three different retroviral genera: the lentiviruses, betaretroviruses and alpharetroviruses. Comparison of the three structures reveals the features of the supramolecular organization of Gag that are conserved between genera and therefore reflect general principles of Gag-Gag interactions and the features that are specific to certain genera. All three Gag proteins assemble to form approximately spherical hexameric lattices with irregular defects. In all three genera, the N-terminal domain of CA is arranged in hexameric rings around large holes. Where the rings meet, 2-fold densities, assigned to the C-terminal domain of CA, extend between adjacent rings, and link together at the 6-fold symmetry axis with a density, which extends toward the center of the particle into the nucleic acid layer. Although this general arrangement is conserved, differences can be seen throughout the CA and spacer peptide regions. These differences can be related to sequence differences among the genera. We conclude that the arrangement of the structural domains of CA is well conserved across genera, whereas the relationship between CA, the spacer peptide region, and the nucleic acid is more specific to each genus.
de Marco
Alex
A
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Davey
Norman E
NE
Ulbrich
Pavel
P
Phillips
Judith M
JM
Lux
Vanda
V
Riches
James D
JD
Fuzik
Tibor
T
Ruml
Tomas
T
Kräusslich
Hans-Georg
HG
Vogt
Volker M
VM
Briggs
John A G
JA
D000595:Amino Acid Sequence; D002460:Cell Line; D017124:Conserved Sequence; D015683:Gene Products, gag / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D006801:Humans; D016093:Mason-Pfizer monkey virus / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D052736:Rous sarcoma virus / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D016415:Sequence Alignment; D014771:Virion / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D019065:Virus Assembly
D015683:Gene Products, gag
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