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
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M R Conte1, M Klikova, E Hunter
1Department of Biochemistry, Imperial College of Science, Technology and Medicine, University of London, London SW7 2AY, UK.
Abstract:
The Mason-Pfizer monkey virus (M-PMV) is the prototype of the type D retroviruses. In type B and D retroviruses, the Gag protein pre-assembles before association with the membrane, whereas in type C retroviruses (lentiviruses, BLV/HTLV group) Gag is targeted efficiently to the plasma membrane, where the particle formation occurs. The N-terminal domain of Gag, the matrix protein (MA), plays a critical role in determining this morphogenic difference. We have determined the three-dimensional solution structure of the M-PMV MA by heteronuclear nuclear magnetic resonance. The protein contains four alpha-helices that are structurally similar to the known type C MA structures. This similarity implies possible common assembly units and membrane-binding mechanisms for type C and B/D retroviruses. In addition to this, the interpretation of mutagenesis data has enabled us to identify, for the first time, the structural basis of a putative intracellular targeting motif.
Insights
The Mason-Pfizer monkey virus matrix protein (MA) structure reveals similarities to type C retroviruses, suggesting common assembly mechanisms. This study identifies the structural basis for an intracellular targeting motif in M-PMV MA.
Area of Science:
- Virology
- Structural Biology
- Molecular Biology
Background:
- Mason-Pfizer monkey virus (M-PMV) is a type D retrovirus.
- Retrovirus particle formation differs between types B/D and C, with Gag assembly occurring pre- or post-membrane association, respectively.
- The N-terminal Gag matrix protein (MA) dictates this morphogenic difference.
Purpose of the Study:
- To determine the three-dimensional solution structure of the M-PMV MA protein.
- To investigate the structural basis for differences in retroviral particle formation.
- To identify the structural basis of an intracellular targeting motif in M-PMV MA.
Main Methods:
- Heteronuclear nuclear magnetic resonance (NMR) spectroscopy to determine the 3D solution structure of M-PMV MA.
- Mutagenesis studies to interpret functional motifs.
Main Results:
- The M-PMV MA structure consists of four alpha-helices.
- The M-PMV MA structure is similar to type C retroviral MA structures.
- Mutagenesis data allowed identification of the structural basis for a putative intracellular targeting motif.
Conclusions:
- Structural similarities between M-PMV (type D) and type C MA proteins suggest conserved assembly units and membrane-binding mechanisms.
- The study provides the first structural insight into an intracellular targeting motif in M-PMV MA, crucial for understanding retroviral morphogenesis.