Identification of Novel Interactions in HIV-1 Capsid Protein Assembly by High-resolution Mass Spectrometry

Lanman, Jason; Lam, TuKiet T.; Barnes, Stephen; Sakalian, Michael; Emmett, Mark R.; Marshall, Alan G.; Prevelige, Peter E.

doi:10.1016/s0022-2836(02)01245-7

Cited by 188 publications

(190 citation statements)

References 50 publications

Supporting

Mentioning

181

Contrasting

Unclassified

Order By: Relevance

“…Gratifyingly, this pseudoatomic model of the hexagonal capsid lattice is consistent with a large body of biochemical and genetic data, including deuterium exchange, crosslinking, mutagenesis, and second-site suppressor studies (e.g., see Fig. 3c and d) [47,58,98,103,104]. Although a molecular model for the hexagonal CA lattice is now in hand, we still lack a comprehensive, high-resolution structural model of the mature HIV-1 capsid.…”

Section: Structure Of the Hexameric Ca Latticesupporting

confidence: 77%

“…(g, h) Secondary structure of the HIV-1 Ψ packaging element (g), and high-resolution structures (h) of the isolated NC domain bound to the second (left) and third (right) Ψ stem loops, with NC in blue and RNA in red [85,86]. Color coding is the same as in (a), except with CA residues colored red to denote sites of significant protection from deuterium exchange in the hexagonal CA lattice [103]. Note that the exposed red patch in (d) corresponds to the …”

Section: Virus Assembly In Vitro and In Vivomentioning

confidence: 99%

See 1 more Smart Citation

The structural biology of HIV assembly

Ganser‐Pornillos

Yeager

Sundquist

2008

Current Opinion in Structural Biology

412

422

View full text Add to dashboard Cite

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.

show abstract

Section: Structure Of the Hexameric Ca Latticesupporting

confidence: 77%

Section: Virus Assembly In Vitro and In Vivomentioning

confidence: 99%

The structural biology of HIV assembly

Ganser‐Pornillos

Yeager

Sundquist

2008

Current Opinion in Structural Biology

412

422

View full text Add to dashboard Cite

show abstract

“…It is possible that the destabilized monomeric capsid can be stabilized by intermolecular hydrophobic interactions between capsids in which Ile 71 has been mutated to Val 71 . This possibility is supported by crystallographic models, mutational analysis, and chemical cross-linking experiments showing that helices 1 to 3 are involved in stabilizing capsid hexamers (33) and that helix 4 may promote the assembly of hexameric oligomers (21).…”

Section: Discussionmentioning

confidence: 89%

Simian-Human Immunodeficiency Virus Escape from Cytotoxic T-Lymphocyte Recognition at a Structurally Constrained Epitope

Peyerl

Barouch

Yeh

et al. 2003

J Virol

View full text Add to dashboard Cite

Virus-specific cytotoxic T lymphocytes (CTL) exert intense selection pressure on replicating simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) in infected individuals. The immunodominant Mamu-A * 01-restricted Gag p11C, C-M epitope is highly conserved among all sequenced isolates of SIV and therefore likely is structurally constrained. The strategies used by virus isolates to mutate away from an immunodominant epitope-specific CTL response are not well defined. Here we demonstrate that the emergence of a position 2 p11C, C-M epitope substitution (T47I) in a simian-human immunodeficiency virus (SHIV) strain 89.6P-infected Mamu-A * 01 ؉ monkey is temporally correlated with the emergence of a flanking isoleucine-to-valine substitution at position 71 (I71V) of the capsid protein. An analysis of the SIV and HIV-2 sequences from the Los Alamos HIV Sequence Database revealed a significant association between any position 2 p11C, C-M epitope mutation and the I71V mutation. The T47I mutation alone is associated with significant decreases in viral protein expression, infectivity, and replication, and these deficiencies are restored to wild-type levels with the introduction of the flanking I71V mutation. Together, these data suggest that a compensatory mutation is selected for in SHIV strain 89.6P to facilitate the escape of that virus from CTL recognition of the dominant p11C, C-M epitope.

show abstract

“…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. We show that the b-hairpin is unfolded and that the protein crystallizes as a dimer.…”

mentioning

confidence: 90%