NMR Structure of the N-Terminal Domain of Capsid Protein from the Mason–Pfizer Monkey Virus

Authors

Macek, P., Chmelik, J., Krizova, I., Kaderavek, P., Padrta, P., Zidek, L., Wildova, M., Hadravova, R., Chaloupkova, R., Pichova, I., Ruml, T., Rumlova, M., Sklenar, V.

Source

JOURNAL OF MOLECULAR BIOLOGY 392: 100-114 (2009)

Abstract

The high-resolution structure of the N-terminal domain (NTD) of the retroviral capsid protein (CA) of Mason–Pfizer monkey virus (M-PMV), a member of the betaretrovirus family, has been determined by NMR. The M-PMV NTD CA structure is similar to the other retroviral capsid structures and is characterized by a six-α-helix bundle and an N-terminal β-hairpin, stabilized by an interaction of highly conserved residues, Pro1 and Asp57. Since the role of the β-hairpin has been shown to be critical for formation of infectious viral core, we also investigated the functional role of M-PMV β-hairpin in two mutants (i.e., ΔP1NTDCA and D57ANTDCA) where the salt bridge stabilizing the wild-type structure was disrupted. NMR data obtained for these mutants were compared with those obtained for the wild type. The main structural changes were observed within the β-hairpin structure; within helices 2, 3, and 5; and in the loop connecting helices 2 and 3. This observation is supported by biochemical data showing different cleavage patterns of the wild-type and the mutated capsid–nucleocapsid fusion protein (CANC) by M-PMV protease. Despite these structural changes, the mutants with disrupted salt bridge are still able to assemble into immature, spherical particles. This confirms that the mutual interaction and topology within the β-hairpin and helix 3 might correlate with the changes in interaction between immature and mature lattices.

Full text

Citation

Macek, P., Chmelik, J., Krizova, I., Kaderavek, P., Padrta, P., Zidek, L., Wildova, M., Hadravova, R., Chaloupkova, R., Pichova, I., Ruml, T., Rumlova, M., Sklenar, V., 2009: NMR Structure of the N-Terminal Domain of Capsid Protein from the Mason–Pfizer Monkey Virus. Journal of Molecular Biology 392: 100-114.

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