| Details: |
In order to function, a cell’s proteins must fold into their native shapes. Cells have multiple chaperones
that work together to help other proteins, their clients, to stay folded and disaggregated. The
chaperone machinery is like a miniature hospital: it assesses the ‘sickness’ of the patient (finds
improperly folded proteins), sends the patient to the right doctor (sorts the sick protein to the right
chaperone), then cures the disease (folds or disaggregates the protein). Although individual parts of
cell’s proteostasis machinery (protein homeostasis) have been studied extensively, the principles of
the full machine are not yet known: How are the sick proteins recognized? Are the routing decisions
made by the clients or by the chaperones? Does the machine shift gears to accommodate different
growth rates? We have developed a proteostasis model of E. coli by combining knowledge of physical
chemistry and system biology. I will describe how the model can uncover various underlying working
principles of a healthy cell. In addition, I will discuss about the protection mechanism of chaperones
from oxidative damage of E. coli proteome. |