Biological complexity: regulating metabolism (Introduction)

by David Turell , Monday, June 22, 2015, 19:40 (3442 days ago) @ David Turell

A description of some the automatic regulators in bacteria:-http://phys.org/news/2015-06-mysteries-bacterial-cell.html-"In bacteria, the cell cycle is very tightly controlled by protein-digesting enzymes called proteases that selectively destroy other proteins, called substrates, at appropriate times while the cell is undergoing growth and division. At the same time, another process called phosphorylation chemically modifies different proteins to regulate their activity in a cell-cycle-dependent way, Chien explains.-"Although the energy-dependent proteases that carry out most protein degradation can directly recognize some substrates, biological regulation often requires additional factors known as adaptors to be present to "tune" substrate selection more precisely. In the bacterium Caulobacter crescentus studied in the Chien lab, one of these adaptors, a small protein called CpdR, is specifically phosphorylated at different times in the cell cycle. Previous studies had shown that the timing of this phosphorylation correlated with the degradation of many proteins by a protease called ClpXP.-"Chien says, "Before this work, we thought most adaptors were binding to the protease and substrate at the same time, effectively leashing them together to force them to interact. Surprisingly, Joanne found that CpdR bound principally to the ClpXP protease, but didn't seem to bind the substrate well at all. Instead, CpdR binding to the ClpXP protease prepared, or primed, the protease for engaging substrates. This primed protease was now also able to recruit additional adaptors that could deliver even more protease substrates."-"He adds, "By not specifically interacting with any single substrate, this new mechanism of protease priming allows for surprisingly broad recognition of both substrates and additional regulators. This mechanism lets the cell control multiple pathways with a single regulator, which is useful when bacteria have to respond rapidly, such as during the stress they undergo when treated with antibiotics. However, this could also lead to unwanted degradation of off-target proteins. Understanding this balance of specificity and broad recognition is an outstanding question.'"