Three-Dimensional Structure of the HTLV-II Matrix Protein and Comparative Analysis of Matrix Proteins from the Different Classes of Pathogenic Human Retroviruses

Christensen, Allyson M.; Massiah, Michael A.; Turner, Brian G.; Sundquist, Wesley I.; Summers, Michael F.

doi:10.1006/jmbi.1996.0700

Cited by 58 publications

(65 citation statements)

References 122 publications

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“…As postulated for other M-proteins (20,29), the basic face of the BDV-M tetramer, interspersed with surface exposed aliphatic and aromatic residues, could facilitate membrane targeting and/or binding, consistent with membrane binding capabilities of the BDV-M tetramer (16). VP40 membrane binding is affected by the C-terminal domains in the hexameric state (9,33) in an as-yet-unknown manner.…”

Section: Discussionmentioning

confidence: 60%

“…Despite a lack of any significant sequence homology among NSV M-proteins, BDV-M exhibits a striking resemblance to the 2 domains of VP40 (17). This conservation of 3D structure in the absence of any recognizable evolutionary relationship is reminiscent of the situation for retroviral M-proteins (29). However, the structures of BDV-M and VP40 are clearly different to those of other NSVs.…”

Section: Discussionmentioning

confidence: 92%

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Crystal structure of the Borna disease virus matrix protein (BDV-M) reveals ssRNA binding properties

Neumann¹,

Lieber²,

Meyer³

et al. 2009

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

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 92%

Crystal structure of the Borna disease virus matrix protein (BDV-M) reveals ssRNA binding properties

Neumann¹,

Lieber²,

Meyer³

et al. 2009

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

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“…On the other hand, we do find it compelling that there is remarkable similarity in the three-dimensional structures of all retroviral MA proteins, each having four major alpha helices separated by flexible loops, with the first two helices overlapping the second two (14,28,38,39). The structures of these evolutionarily diverse MA proteins are conserved even though the mechanisms that they use for membrane binding are not (e.g., the requirements for myristate and the clustering of basic residues differ for RSV and HIV) (55,63).…”

Section: Discussionmentioning

confidence: 68%

RNA Dimerization Defect in a Rous Sarcoma Virus Matrix Mutant

Parent

Cairns

Albert³

et al. 2000

J Virol

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The retrovirus matrix (MA) sequence of the Gag polyprotein has been shown to contain functions required for membrane targeting and binding during particle assembly and budding. Additional functions for MA have been proposed based on the existence of MA mutants in Rous sarcoma virus (RSV), murine leukemia virus, human immunodeficiency virus type 1, and human T-cell leukemia virus type 1 that lack infectivity even though they release particles of normal composition. Here we describe an RSV MA mutant with a surprising and previously unreported phenotype. In the mutant known as Myr1E, the small membrane-binding domain of the Src oncoprotein has been added as an N-terminal extension of Gag. While Myr1E is not infectious, full infectivity can be reestablished by a single amino acid substitution in the Src sequence (G2E), which eliminates the addition of myristic acid and the membrane-binding capacity of this foreign sequence. The presence of myristic acid at the N terminus of the Myr1E Gag protein does not explain its replication defect, because other myristylated derivatives of RSV Gag are fully infectious (e.g., Myr2 [C. R. Erdie and J. W. Wills, J. Virol. 64:5204-5208, 1990]). Biochemical analyses of Myr1E particles reveal that they contain wild-type levels of the Gag cleavage products, Env glycoproteins, and reverse transcriptase activity when measured on an exogenous template. Genomic RNA incorporation appears to be mildly reduced compared to the wild-type level. Unexpectedly, RNA isolated from Myr1E particles is monomeric when analyzed on nondenaturing Northern blots. Importantly, the insertional mutation does not lie within previously identified dimer linkage sites. In spite of the dimerization defect, the genomic RNA from Myr1E particles serves efficiently as a template for reverse transcription as measured by an endogenous reverse transcriptase assay. In marked contrast, after infection of avian cells, the products of reverse transcription are nearly undetectable. These findings might be explained either by the loss of a normal function of MA needed in the formation or stabilization of RNA dimers or by the interference in such events by the mutant MA molecules. It is possible that Myr1E viruses package a single copy of viral RNA.The retrovirus Gag polyprotein directs the assembly and budding of virus particles from the plasma membrane of infected cells. Extensive functional mapping of several Gag proteins has led to the identification of three common assembly domains that are required for this activity. The N-terminal membrane-binding (M) domain directs Gag molecules from the cytoplasm to the inner leaflet of the plasma membrane (44,55,63) where aggregates of Gag proteins are formed through protein-protein interactions primarily involving the I (interaction) domains (4, 12, 22, 57). These interactions lead to the emergence of spherical particles that pinch off the membrane during the final step in the budding process, which is mediated by the L (late) assembly domain (27,45,58). Virus maturation occurs as the...

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“…One possible interpretation is that the tight viral PM interaction of the HIV-1 MA in the HIV/HIV-C and HIV/HTLV CA chimeric Gag proteins results in the deformation of the lipid bilayer. A second possible interpretation is that the C terminus of the HIV-1 MA is less flexible than the C terminus of deltaretroviral MA domains, which would allow the flat regions of HTLV-1 lattice to have less of an impact on the VLP shape (47).…”

Section: Discussionmentioning

confidence: 99%

Disparate Contributions of Human Retrovirus Capsid Subdomains to Gag-Gag Oligomerization, Virus Morphology, and Particle Biogenesis

Martin

Mendonça

Angert

et al. 2017

J Virol

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The capsid domain (CA) of the retroviral Gag protein is a primary determinant of Gag oligomerization, which is a critical step for immature Gag lattice formation and virus particle budding. Although the human immunodeficiency virus type 1 (HIV-1) CA carboxy-terminal domain (CTD) is essential for CA-CA interactions, the CA CTD has been suggested to be largely dispensable for human T-cell leukemia virus type 1 (HTLV-1) particle biogenesis. To more clearly define the roles of the HTLV-1 CA amino-terminal domain (NTD) and CA CTD in particle biogenesis, we generated and analyzed a panel of Gag proteins with chimeric HIV-1/HTLV-1 CA domains. Subcellular distribution and protein expression levels indicated that Gag proteins with a chimeric HIV-1 CA NTD/HTLV-1 CA CTD did not result in Gag oligomerization regardless of the parent Gag background. Furthermore, chimeric Gag proteins with the HTLV-1 CA NTD produced particles phenotypically similar to HTLV-1 immature particles, highlighting the importance of the HTLV-1 CA NTD in HTLV-1 immature particle morphology. Taken together, these observations support the conclusion that the HTLV-1 CA NTD can functionally replace the HIV-1 CA CTD, but the HIV-1 CA NTD cannot replace the HTLV-1 CA CTD, indicating that the HTLV-1 CA subdomains provide distinct contributions to Gag-Gag oligomerization, particle morphology, and biogenesis. Furthermore, we have shown for the first time that HIV-1 and HTLV-1 Gag domains outside the CA (e.g., matrix and nucleocapsid) impact Gag oligomerization as well as immature particle size and morphology. IMPORTANCE A key aspect in virus replication is virus particle assembly, which is a poorly understood process for most viruses. For retroviruses, the Gag structural protein is the primary driver of virus particle biogenesis, and the CA CTD is the primary determinant of Gag-Gag interactions for HIV-1. In this study, the HTLV-1 capsid amino-terminal domain was found to provide distinct contributions to Gag-Gag oligomerization, particle morphology, and biogenesis. This study provides information that will aid efforts for discovery of therapeutic targets for intervention.

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Three-Dimensional Structure of the HTLV-II Matrix Protein and Comparative Analysis of Matrix Proteins from the Different Classes of Pathogenic Human Retroviruses

Cited by 58 publications

References 122 publications

Crystal structure of the Borna disease virus matrix protein (BDV-M) reveals ssRNA binding properties

Crystal structure of the Borna disease virus matrix protein (BDV-M) reveals ssRNA binding properties

RNA Dimerization Defect in a Rous Sarcoma Virus Matrix Mutant

Disparate Contributions of Human Retrovirus Capsid Subdomains to Gag-Gag Oligomerization, Virus Morphology, and Particle Biogenesis

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