Retrovirus Capsid Protein Assembly Arrangements

Mayo, Keith; Huseby, Douglas L.; McDermott, Jason; Arvidson, Brian; Finlay, Liam; Barklis, Eric

doi:10.1016/s0022-2836(02)01176-2

Cited by 68 publications

(93 citation statements)

References 64 publications

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“…b, The mature particle. The relative position of the NTD and CTD of CA are as observed by Li et al 4 and Mayo et al 5 The two CA molecules shown would form part of a hexagonal array viewed from the side. molecules be packed and what structural changes might occur during maturation?…”

Section: Resultssupporting

confidence: 54%

“…2,3 After maturation, MA associates with the viral membrane, CA forms the shell of the mature core, and NC associates with the genomic RNA and other virally coded enzymes required for RNA replication inside the CA shell. Whereas the CA -CA contacts in the mature core of HIV-1 have been modeled with respect to a cryo-electron microscopic (cryoEM) reconstruction 4 and electron crystallography of two-dimensional crystals, 5,6 much less is known about the Gag -Gag contacts in immature retrovirus cores. 7,8 The morphogenetic changes in the Gag particle can be mimicked by in vitro assembly of Gag or modified Gag proteins.…”

Section: Introductionmentioning

confidence: 99%

“…This model is also consistent with electron diffraction from two-dimensional crystals. 5,6 However, although they were not envisioned in the original model, apparently heterotypic NTD -CTD contacts also occur. 25 It is unclear to what extent this structure of the mature core reflects the organization of Gag molecules in immature particles, although the latter also appears to be built on a hexagonal lattice, 5,26 Here, we report the structure of the RSV CA protein NTD extended by the 25 amino acid residues that are upstream of CA in Gag.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Dimeric Rous Sarcoma Virus Capsid Protein Structure Relevant to Immature Gag Assembly

Nandhagopal

Simpson

Johnson

et al. 2004

Journal of Molecular Biology

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Section: Resultssupporting

confidence: 54%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Dimeric Rous Sarcoma Virus Capsid Protein Structure Relevant to Immature Gag Assembly

Nandhagopal

Simpson

Johnson

et al. 2004

Journal of Molecular Biology

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“…Nevertheless, further studies will be required to confirm these models and provide molecular details of the intra-and interhexamer contacts in the immature HIV-1 Gag lattice. In this regard, considerable insight will likely be gleaned from higher resolution structural studies of immature HIV-1, MLV, and MPMV (Mazon-Pfizer monkey virus) Gag assemblies formed in vitro [62][63][64][65], and from deuterium-exchange protection experiments that map protein-protein interfaces in the immature lattice (P. Prevelige, pers. comm.…”

Section: Gag-gag Lattice Interactions In the Immature Virion Are Medimentioning

confidence: 99%

The structural biology of HIV assembly

Ganser‐Pornillos

Yeager

Sundquist

2008

Current Opinion in Structural Biology

412

422

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HIV assembly and replication proceed through formation of morphologically distinct immature and mature viral capsids that are organized by the Gag polyprotein (immature) and by the fully processed CA protein (mature). The Gag polyprotein is composed of three folded polypeptides (MA, CA, and NC) and three smaller peptides (SP1, SP2, and p6) that function together to coordinate membrane binding and Gag-Gag lattice interactions in immature virions. Following budding, HIV maturation is initiated by proteolytic processing of Gag, which induces conformational changes in the CA domain and results in assembly of the distinctive conical capsid. Retroviral capsids are organized following the principles of fullerene cones, and the hexagonal CA lattice is stabilized by three distinct interfaces. Recently identified inhibitors of viral maturation act by disrupting the final stage of Gag processing, or by inhibiting formation of a critical intermolecular CA-CA interface in the mature capsid. Following release into a new host cell, the capsid disassembles and host cell factors can potently restrict this stage of retroviral replication. Here, we review the structures of immature and mature HIV virions, focusing on recent studies that have defined the global organization of the immature Gag lattice, identified sites likely to undergo conformational changes during maturation, revealed the molecular structure of the mature capsid lattice, demonstrated that capsid architectures are conserved, identified the first capsid assembly inhibitors, and begun to uncover the remarkable biology of the mature capsid.

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“…These CTD interactions, at least in part, involve a well-characterized dimer interface accommodated by helix 9. Formation of the hexagonal lattice may represent a basic principle not only for the construction of capsid cores within mature particles but also for the generation of immature virus by the Gag precursor (32,33).…”

mentioning

confidence: 99%

Mutation of the SP1 Sequence Impairs both Multimerization and Membrane-Binding Activities of Human Immunodeficiency Virus Type 1 Gag

Guo

Roldán

et al. 2005

J Virol

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The Gag protein of human immunodeficiency virus type 1 contains a 14-amino-acid region, termed SP1, between the capsid and downstream nucleocapsid sequences. Although SP1 is known to be indispensable for virus production, the mechanisms involved are mostly unclear. In this study, we demonstrate that an M368A mutation within SP1 severely diminished the ability of Gag to associate with cellular membranes. Although wild-type levels of membrane binding were restored to the M368A Gag by a second-site L20K mutation within matrix, the resultant Gag mutant L20K-M368A remained defective in virus production. This latter deficit was partially consequent to the binding of L20K-M368A Gag to nonraft membranes as opposed to raft association seen for wild-type Gag. Further analysis revealed that the majority of membrane-bound M368A Gag proteins were small oligomers, indicating a multimerization defect. In support of this observation, purified recombinant Gag derivatives containing the M368A mutation formed much lower amounts of high-molecular-weight complexes that were pelletable at 21,000 ؋ g than did wild-type Gag. Based on the myristyl switch model, we propose that the M368A mutation inhibits Gag multimerization and, as a result, restricts the binding of Gag to cellular membranes.

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Retrovirus Capsid Protein Assembly Arrangements

Cited by 68 publications

References 64 publications

Dimeric Rous Sarcoma Virus Capsid Protein Structure Relevant to Immature Gag Assembly

Dimeric Rous Sarcoma Virus Capsid Protein Structure Relevant to Immature Gag Assembly

The structural biology of HIV assembly

Mutation of the SP1 Sequence Impairs both Multimerization and Membrane-Binding Activities of Human Immunodeficiency Virus Type 1 Gag

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