A single-point mutation of M-PMV matrix protein causes reorientation of protein domains and changes the phenotype of the virus


Jiří Vlach1, Jan Lipov2, Václav Veverka1, Jan Lang1,3, Pavel Srb3,
Michaela Rumlová4, Eric Hunter5, Tomáš Ruml2,4, and Richard Hrabal1


1 Laboratory of NMR Spectroscopy (vlachj@vscht.cz)

2Department of Biochemistry and Microbiology

Institute of Chemical Technology Prague, Technická 5, 166 28 Prague, Czech Republic

3Department of Low Temperature Physics, Faculty of Mathematics and Physics, Charles University, 180 00 Prague, Czech Republic

4Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech republic, Flemingovo nám. 2, 166 10, Prague, Czech Republic

5Yerkes Natural Primate Research Center, Emory Vaccine Center, 954 Gatewood Road, Atlanta GA 30329 USA


Mason-Pfizer monkey virus (M-PMV) is a representative member of D-type retrovirus family. Characteristic feature of this family is the location of assembly of new virions which occurs in the pericentriolar region of an infected cell. It is the matrix protein (MA) – the N-terminal part of Gag polyprotein – that is responsible for directing the assembly of Gag polyproteins to the site of assembly [1]. MA protein interacts with Tctex-1, the light chain from a dynein molecular motor, and the Gag can then be transported in a complex with dynein [2]. If we introduce mutation R55F or R55W to the MA, the viral capsids are no longer assembled in the pericentriolar region, but at the inner side of the plasma membrane [3]. This modified behavior is typical for C-type retroviruses (e. g. HIV-1).

We present here 3D structures of the wild type MA and its R55F mutant solved by NMR spectroscopy. The comparison of both structures revealed a completely different orientation of N- and C-terminal domains, while the local structure within the domains remained conserved. The reorientation causes that part of the linker (residues 42–52) between both domains becomes hidden, therefore the interaction with Tctex-1 is prevented. The results are supported by 15N relaxation measurements.

We thank the Grant Agency of the Czech Republic for the financial support (Grant 203/03/0490).

1.     E. O. Freed, Journal Of Virology, 76, (2002), 4679–4687.

2.     S. S. Rhee, unpublished results.

3.     S. S. Rhee and E. Hunter, Cell, 63, (1990), 77–86.