The three-dimensional solution structure of the matrix protein from the type D retrovirus, the Mason–Pfizer monkey virus, and implications for the morphology of retroviral assembly

Conte, Maria R.; Klikova, M.; Hunter, Eric; Ruml, Tomáš; Matthews, Stephen

doi:10.1093/emboj/16.19.5819

Cited by 57 publications

(47 citation statements)

References 41 publications

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“…A conceptual three-dimensional model of the M-PMV matrix protein containing myristic acid was generated by molecular graphics. The position of myristic acid in the model was obtained by superimposing the protein coordinates of myristylated recoverin in the calcium-free state onto the nonmyristylated M-PMV structure with the program O (9,15,38). The molecular surface for myristic acid and the M-PMV ribbon diagram were generated with the program Ribbons (7).…”

Section: Methodsmentioning

confidence: 99%

“…Based on the distribution of anti-p12, wild-type M-PMV- (37) was modeled into the NMR structure of the nonmyristylated M-PMV matrix protein (9). The side chains of tyrosine residues 11, 28, and 67 are oriented toward the hydrophobic interior of the matrix protein, while the side chain of tyrosine 82 is oriented away from the core.…”

Section: Construction Of M-pmv Matrix Mutantsmentioning

confidence: 99%

“…Based on a nuclear magnetic resonance (NMR) analysis of the M-PMV matrix protein, which is comprised of four helical domains arranged in two perpendicularly aligned pairs (9), and on an MA mutant (T41I/T78I) that accumulated immature capsids at the plasma membrane (25), it was previously hypothesized that the myristic acid moiety is sequestered within the MA domain prior to plasma membrane interactions (9). T41I/ T78I immature capsids are assembled and transported to the plasma membrane with wild-type kinetics but are defective at an early stage of budding (25).…”

mentioning

confidence: 99%

“…T41I/ T78I immature capsids are assembled and transported to the plasma membrane with wild-type kinetics but are defective at an early stage of budding (25). Because the structural analyses showed that both of the threonine residues replaced in this mutant are oriented toward the core of the matrix protein, it was reasoned that substitution with the hydrophobic isoleucine residues might prevent release of myristic acid from the more hydrophobic MA core, even after the T41I/T78I capsid interacted with the lipid bilayer (9).…”

mentioning

confidence: 99%

“…The presence of myristic acid and a basic domain on many retroviral MA proteins raises the possibility that an electrostatic switch mechanism similar to that of the MARCKS protein occurs during Gag-membrane interactions (9,21,35). HIV type 1 (HIV-1) assembles capsids at the plasma membrane, where the structural Gag polyprotein must associate with the lipid bilayer.…”

mentioning

confidence: 99%

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An Early Stage of Mason-Pfizer Monkey Virus Budding Is Regulated by the Hydrophobicity of the Gag Matrix Domain Core

Stansell

Tytler

Walter

et al. 2004

J Virol

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Intracellular capsid transport and release of Mason-Pfizer monkey virus are dependent on myristylation of the Gag matrix domain (MA). A myristylated MA mutant, in which Thr41 and Thr78 are replaced with isoleucines, assembles capsids that are transported to the plasma membrane but are blocked in an early budding step. Since the nuclear magnetic resonance structure of MA showed that these Thr residues point into the hydrophobic core of the protein, it was hypothesized that the T41I/T78I mutant was defective in release of myristic acid from the more hydrophobic core. In order to further investigate whether an increase in the hydrophobicity of the MA core modulates capsid-membrane interactions and viral budding, three tyrosine residues (11, 28, and 67), oriented toward the MA core, were replaced individually or in a pair-wise combination with the more hydrophobic phenylalanine residue(s). As a control, Tyr82, oriented toward the outer surface of MA, was also replaced with phenylalanine. These Tyr-to-Phe substitutions did not alter capsid assembly compared to wild type in a capsid assembly assay. Pulse-chase, immunofluorescence, and electron microscopy studies demonstrated that single substitutions of Tyr11, Tyr28, and Tyr67 recapitulated the T41I/T78I mutant phenotype of decreased budding kinetics and accumulation of capsids at the plasma membrane. MA double mutants with a combination of these Tyr substitutions exhibited a phenotype that was even more defective in budding. In contrast, MA mutants with Tyr82 replaced by Phe resulted in a transportdefective phenotype. These results strongly support the hypothesis that myristic acid is sequestered inside MA prior to capsid-membrane interactions.

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Section: Methodsmentioning

confidence: 99%

Section: Construction Of M-pmv Matrix Mutantsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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An Early Stage of Mason-Pfizer Monkey Virus Budding Is Regulated by the Hydrophobicity of the Gag Matrix Domain Core

Stansell

Tytler

Walter

et al. 2004

J Virol

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Solution structure and backbone dynamics of Mason‐Pfizer monkey virus (MPMV) nucleocapsid protein

1998

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Retroviral nucleocapsid proteins (NCPs) are CCHC-type zinc finger proteins that mediate virion RNA binding activities associated with retrovirus assembly and genomic RNA encapsidation. Mason-Pfizer monkey virus (MPMV), a type D retrovirus, encodes a 96-amino acid nucleocapsid protein, which contains two Cys-X2-Cys-X4-His-X4-Cys (CCHC) zinc fingers connected by an unusually long 15-amino acid linker. Homonuclear, two-dimensional sensitivity-enhanced l5N-'H. three-dimensional "N-IH, and triple resonance NMR spectroscopy have been used to determine the solution structure and residue-specific backbone dynamics of the structured core domain of MPMV NCP containing residues 2 1-80. Structure calculations and spectral density mapping of N-H bond vector mobility reveal that MPMV NCP 2 1-80 is best described as two independently folded, rotationally uncorrelated globular domains connected by a seven-residue flexible linker consisting of residues 42-48. The N-terminal CCHC zinc finger domain (residues 24-37) appears to adopt a fold like that described previously for HIV-1 NCP; however, residues within this domain and the immediately adjacent linker region (residues 38-41) are characterized by extensive conformational averaging on the ps-ms time scale at 25 "C. In contrast to other NCPs, residues 49-77, which includes the C-terminal CCHC zinc-finger (residues 53-66). comprise a well-folded globular domain with the Val49-Pro-Gly-Leu52 sequence and C-terminal tail residues 67-77 characterized by amide proton exchange properties and "N RI, R2, and {'H-I'NN) NOE values indistinguishable to residues in the core C-terminal finger. Twelve refined structural models of MPMV NCP residues 49-80 (pairwise backbone RMSD of 0.77 A) reveal that the side chains of the conserved Pro50 and Trp62 are in van der Waals contact with one another. Residues 70-73 in the C-terminal tail adopt a reverse turn-like structure. Ile77 is involved in extensive van der Waals contact with the core finger domain, while the side chains of Ser68 and Am75 appear to form hydrogen bonds that stabilize the overall fold of this domain. These residues outside of the core finger structure are conserved in D-type and related retroviral NCPs, e.g., MMTV NCP, suggesting that the structure of MPMV NCP may be representative of this subclass of retroviral NCPs. Keywords:Mason-Pfizer monkey virus (MPMV) is the prototypical member of the primate D-type retroviruses that include simian AIDS retrovirus type 1 (SRV-I) and SRV-2, the causative agents of simian AIDS in captive macaque populations (Power et al., 1986). Mouse mammary tumor virus (MMTV) is a type B retrovirus most closely

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Structural characterization and membrane binding properties of the matrix protein VP40 of ebola virus

Ruigrok

Schoehn

Dessen

et al. 2000

Journal of Molecular Biology

145

196

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The three-dimensional solution structure of the matrix protein from the type D retrovirus, the Mason–Pfizer monkey virus, and implications for the morphology of retroviral assembly

Cited by 57 publications

References 41 publications

An Early Stage of Mason-Pfizer Monkey Virus Budding Is Regulated by the Hydrophobicity of the Gag Matrix Domain Core

An Early Stage of Mason-Pfizer Monkey Virus Budding Is Regulated by the Hydrophobicity of the Gag Matrix Domain Core

Solution structure and backbone dynamics of Mason‐Pfizer monkey virus (MPMV) nucleocapsid protein

Structural characterization and membrane binding properties of the matrix protein VP40 of ebola virus

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