Protein oligomerization and backbone flexibility.

Pavel Srb^1,2, Jan Prchal^2,3, Jiří Vlach² Jan Lang ^1,2, Marián Grocký¹, Jan, Tomáš Ruml³ and Richard Hrabal²

¹Department of Low Temperature Physics, Faculty of Mathematics and Physics, Charles University, V Holešovičkách 2, 180 00 Prague 8, Czech Republic

²Laboratory of NMR Spectroscopy and

³Department of Biochemistry and Microbiology

Institute of Chemical Technology, Technická 5, 166 28 Prague 6, Czech Republic

richard.hrabal@vscht.cz

Oligomerization capacity of the retroviral matrix protein is an important feature that affects assembly of immature virions and their interaction with cellular membrane. A combination of NMR relaxation measurements and advanced analysis of molecular dynamics simulation trajectory provided an unprecedentedly detailed insight into internal mobility of matrix proteins of the Mason-Pfizer monkey virus. Strong evidences have been obtained that the oligomerization capacity of the wild type matrix protein is closely related to the enhanced dynamics of several parts of its backbone on ns timescale. Increased flexibility has been observed for two regions: the loop between α-helices α2 and α3 and the C-terminal half of α-helix α3 which accommodate amino acid residues that form the oligomerization interface. On the other hand, matrix mutant R55F that has changed structure and does not exhibit any specific oligomerization in solution was found considerably more rigid. Our results document that conformational selection mechanism together with induced fit and favorable structural pre-organization play an important role in the control of the oligomerization process.

[1] J. Vlach, et al. J. Mol. Biol., 390, 5, 967-980, (2009)

[2] P. Srb, et al., J.Phys.Chem.B., accepted, (2011)