title: The effect of point mutations within the N-terminal domain of Mason-Pfizer monkey virus capsid protein on virus core assembly and infectivity.
abstract: Retroviral capsid protein (CA) mediates protein interactions driving the assembly of both immature viral particles and the core of the mature virions. Structurally conserved N-terminal domains of several retroviruses refold after proteolytic cleavage into a beta-hairpin, stabilized by a salt bridge between conserved N-terminal Pro and Asp residues. Based on comparison with other retroviral CA, we identified Asp50 and Asp57 as putative interacting partners for Pro1 in Mason-Pfizer monkey virus (M-PMV) CA. To investigate the importance of CA Pro1 and its interacting Asp in M-PMV core assembly and infectivity, P1A, P1Y, D50A, T54A and D57A mutations were introduced into M-PMV. The P1A and D57A mutations partially blocked Gag processing and the released viral particles exhibited aberrant cores and were non-infectious. These data indicate that the region spanning residues Asp50-Asp57 plays an important role in stabilization of the beta-hairpin and that Asp57 likely forms a salt-bridge with P1 in M-PMV CA.
authors.affiliation: Gilead Sciences and IOCB Research Centre, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Marcela
authors.initials: M
authors.lastname: Wildová
authors.forename: Romana
authors.initials: R
authors.lastname: Hadravová
authors.forename: Jitka
authors.initials: J
authors.lastname: Stokrová
authors.forename: Ivana
authors.initials: I
authors.lastname: Krízová
authors.forename: Tomás
authors.initials: T
authors.lastname: Ruml
authors.forename: Eric
authors.initials: E
authors.lastname: Hunter
authors.forename: Iva
authors.initials: I
authors.lastname: Pichová
authors.forename: Michaela
authors.initials: M
authors.lastname: Rumlová