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In 1969, scientist Michael Cashel was analyzing the compounds produced by starved bacteria when he noticed two spots appearing on his chromatogram as if by magic. Today, we know one of these "magic spots," as researchers call them, as guanosine tetraphosphate, or ppGpp for short. We also understand that it is a signaling molecule present in virtually all bacteria, helping tune cell growth and size based on nutrient availability.
And yet, despite decades of study, precisely how ppGpp regulates bacterial growth has remained rather mysterious. Delving further requires a more comprehensive list of the molecules that ppGpp binds to exert its effects.
Collaborators - MIT - Departments - Biology - Chemistry
Now, collaborators from MIT's departments of Biology and Chemistry have developed a method to do just that, and used their new approach to pinpoint over 50 ppGpp targets in Escherichia coli—roughly half which had not been identified previously. Many of these targets are enzymes required to produce nucleotides, the building blocks of DNA and RNA. During times when the bacteria do not have enough nutrients to grow and divide normally, the researchers propose that ppGpp prevents these enzymes from creating new nucleotides from scratch, helping cells enter a dormant state.
"With small molecules or metabolites like ppGpp, it's been difficult historically to determine which proteins they bind," says Michael Laub, a professor of biology, a Howard Hughes Medical Institute investigator, and the senior author of the study. "This has been an intractable problem that's held the field back for some time, but our new approach allows you to nail down the likely targets in a matter of weeks."
Postdoc - Boyuan - Wang - Author - Study
Postdoc Boyuan Wang is the first author of the study, which appears in Nature Chemical Biology on Dec. 17.
Since ppGpp was discovered nearly 50 years ago, it has been shown to suppress DNA replication, transcription, translation, and various metabolic pathways. It puts the brakes...
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