Fullerene-like Organization of HIV gag-Protein Shell in Virus-like Particles Produced by Recombinant Baculovirus

Nermut, M. V.; Hockley, David J.; Jowett, Jeremy B. M.; Jones, Ian M.; Garreau, Mireille; Thomas, Daniel

doi:10.1006/viro.1994.1032

Cited by 123 publications

(138 citation statements)

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“…However, the blocking of Env incorporation can in turn be overcome by deletions in the long cytoplasmic tail of Env (13,14,17,32). These results support the notion that the long cytoplasmic tail of the trimeric Env has to fit the cage hole present in the lattice-like MA trimeric structure during virus assembly (20,38). Nevertheless, whether the reduced Env incorporation observed with these mutants correlates with impaired Env-Gag interaction in cells was not addressed in those studies.…”

supporting

confidence: 50%

Effect of Extension of the Cytoplasmic Domain of Human Immunodeficiency Type 1 Virus Transmembrane Protein gp41 on Virus Replication

Chan

Wang

Lin

et al. 2004

J Virol

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The biological significance of the presence of a long cytoplasmic domain in the envelope (Env) transmembrane protein gp41 of human immunodeficiency virus type 1 (HIV-1) is still not fully understood. Here we examined the effects of cytoplasmic tail elongation on virus replication and characterized the role of the C-terminal cytoplasmic tail in interactions with the Gag protein. Extensions with six and nine His residues but not with fewer than six His residues were found to severely inhibit virus replication through decreased Env electrophoretic mobility and reduced Env incorporation compared to the wild-type virus. These two mutants also exhibited distinct N glycosylation and reduced cell surface expression. An extension of six other residues had no deleterious effect on infectivity, even though some mutants showed reduced Env incorporation into the virus and/or decreased cell surface expression. We further show that these elongated cytoplasmic tails in a format of the glutathione S-transferase fusion protein still interacted effectively with the Gag protein. In addition, the immediate C terminus of the cytoplasmic tail was not directly involved in interactions with Gag, but the region containing the last 13 to 43 residues from the C terminus was critical for Env-Gag interactions. Taken together, our results demonstrate that HIV-1 Env can tolerate extension at its C terminus to a certain degree without loss of virus infectivity and Env-Gag interactions. However, extended elongation in the cytoplasmic tail may impair virus infectivity, Env cell surface expression, and Env incorporation into the virus.

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supporting

confidence: 50%

Effect of Extension of the Cytoplasmic Domain of Human Immunodeficiency Type 1 Virus Transmembrane Protein gp41 on Virus Replication

Chan

Wang

Lin

et al. 2004

J Virol

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“…While the competition binding experiments reported here do not provide rigorous evidence that this can occur they demonstrate that the two classes of RNA ligands do not inhibit each other from binding to gag. The ability of matrix and nucleocapsid ligands to bind simultaneously to gag might be expected since matrix and nucleocapsid are at opposite ends of an elongated protein reported to be ∼85 Å long and 35 Å wide (40).…”

Section: Discussionmentioning

confidence: 99%

In vitro selection of RNAs that bind to the human immunodeficiency virus type-1 gag polyprotein

Lochrie

Waugh²,

Pratt³

et al. 1997

Nucleic Acids Research

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“…After ribosomal translation of viral genes, the p17 domain directs HIV-1 Gag polyproteins to the plasma membrane of the host cell, where assembly and budding of virions occur (2)(3)(4). Excised proteolytically during and immediately after budding of virus particles, p17 forms a protective shell associated directly with the inner leaflet of the viral membrane (5,6). In the early stages of the HIV-1 life cycle, p17 also can dissociate from the viral membrane and direct the core-derived preintegration complex to the host-cell nucleus (7)(8)(9), although the precise role of p17 in regulating HIV-1 nuclear import and enabling the virus to replicate in nondividing cells remains controversial (10)(11)(12)(13)(14).…”

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confidence: 99%

Total chemical synthesis of N-myristoylated HIV-1 matrix protein p17: Structural and mechanistic implications of p17 myristoylation

Alexandratos

Ericksen

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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The HIV-1 matrix protein p17, excised proteolytically from the N terminus of the Gag polyprotein, forms a protective shell attached to the inner surface of the plasma membrane of the virus. During the late stages of the HIV-1 replication cycle, the N-terminally myristoylated p17 domain targets the Gag polyprotein to the host-cell membrane for particle assembly. In the early stages of HIV-1 replication, however, some p17 molecules dissociate from the viral membrane to direct the preintegration complex to the host-cell nucleus. These two opposing targeting functions of p17 require that the protein be capable of reversible membrane interaction. It is postulated that a significant structural change in p17 triggered by proteolytic cleavage of the Gag polyprotein sequesters the N-terminal myristoyl group, resulting in a weaker membrane binding by the matrix protein than the Gag precursor. To test this ''myristoyl switch'' hypothesis, we obtained highly purified synthetic HIV-1 p17 of 131 amino acid residues and its N-myristoylated form in large quantity. Both forms of p17 were characterized by circular dichroism spectroscopy, protein chemical denaturation, and analytical centrifugal sedimentation. Our results indicate that although N-myristoylation causes no spectroscopically discernible conformational change in p17, it stabilizes the protein by 1 kcal͞ mol and promotes protein trimerization in solution. These findings support the premise that the myristoyl switch in p17 is triggered not by a structural change associated with proteolysis, but rather by the destabilization of oligomeric structures of membranebound p17 in the absence of downstream Gag subdomains.

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Fullerene-like Organization of HIV gag-Protein Shell in Virus-like Particles Produced by Recombinant Baculovirus

Cited by 123 publications

References 0 publications

Effect of Extension of the Cytoplasmic Domain of Human Immunodeficiency Type 1 Virus Transmembrane Protein gp41 on Virus Replication

Effect of Extension of the Cytoplasmic Domain of Human Immunodeficiency Type 1 Virus Transmembrane Protein gp41 on Virus Replication

In vitro selection of RNAs that bind to the human immunodeficiency virus type-1 gag polyprotein

Total chemical synthesis of N-myristoylated HIV-1 matrix protein p17: Structural and mechanistic implications of p17 myristoylation

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