Article: Published in Physical Review X by Rafael Delgado-Buscalioni and Pedro J. de Pablo, members of Theoretical Condensed Matter Physics Department, Condensed Matter Physics Department and IFIMAC researchers.
Virus particles consist of a protein shell, known as a capsid, that protects its genome from harsh environmental conditions during transmission from host to host. Once inside a cell, the virus sheds its capsid and releases its DNA. Here, we reveal dynamics of this disassembly that allow virus particles to transfer their genome at the right time and place.
Each of the vertices in these polyhedral capsids are formed by proteins known as pentons. Inside a host cell, the virus finely tunes the sequential loss of pentons to render a semidisrupted capsid at the nuclear pore. Viruses with too many pentons would not be able to release their DNA through the cell’s nuclear pore, whereas those with too few pentons would liberate their genome before reaching the nucleus.
We induce penton failure by applying mechanical fatigue on individual virus particles with atomic force microscopy, which mimics the stresses the virus sustains during its journey to the nucleus. Our approach allows us to study the transition kinetics of penton release as a two-state process, from which we derive the spontaneous escape rate and the free energy barrier of a penton. Moreover, survival analysis shows that the loss of one penton increases the release rate of the remaining ones. This aging process accelerates the overall penton escape rate by about 50% with respect to a sequence of independent escape events.
This “aging” effect, demonstrated for the first time in a biomolecular assembly, evidences a cooperative process involving pentons separated by 45 nm, which is probably the largest range ever found in molecular interactions. [Full article]