TCB Publications - Abstract
Lela Vukovic, Christophe Chipot, Debora L. Makino, Elena Conti, and Klaus Schulten. Molecular mechanism of processive 3' to 5' RNA translocation in the active subunit of the RNA exosome complex. Journal of the American Chemical Society, 138:4069-4078, 2016. (PMC: PMC4988868)
to 5 degradation of RNA molecules,
performed by the exosome complex. ssRNA is channeled through its multi-subunit ring-like core
into the active site tunnel of its key exonuclease subunit Rrp44, which acts both as an enzyme and
a motor. Even in isolation, Rrp44 can pull and sequentially cleave RNA nucleotides, one at a time,
without any external energy input, and release a nal 3-5 nucleotide long product. Using molecular
dynamics simulations, we identify the main factors that control these processes. Our free energy
calculations reveal that RNA transfer from solution into the active site of Rrp44 is highly favorable,
but dependent on the length of the RNA strand. While RNA strands formed by 5 nucleotides or
more correspond to a decreasing free energy along the translocation coordinate towards the cleavage
site, a 4-nucleotide RNA experiences a free energy barrier along the same direction, potentially
leading to incomplete cleavage of ssRNA and the release of short (3-5) nucleotide products. We
provide a new insight into how Rrp44 catalyzes a localized enzymatic reaction, and performs an
action distributed over several RNA nucleotides, leading eventually to the translocation of whole
RNA segments into the position suitable for cleavage.
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