Abstract:
:Bacteria tightly regulate intracellular zinc levels to ensure sufficient zinc to support essential functions, while preventing toxicity. The bacterial response to zinc limitation includes the expression of putative zinc metallochaperones belonging to subfamily 1 of the COG0523 family of G3E GTPases. However, the client proteins and the metabolic processes served by these chaperones are unclear. Here, we demonstrate that the Bacillus subtilis YciC zinc metallochaperone (here renamed ZagA for ZTP activated GTPase A) supports de novo folate biosynthesis under conditions of zinc limitation, and interacts directly with the zinc-dependent GTP cyclohydrolase IA, FolE (GCYH-IA). Furthermore, we identify a role for the alarmone ZTP, a modified purine biosynthesis intermediate, in the response to zinc limitation. ZTP, a signal of 10-formyl-tetrahydrofolate (10f-THF) deficiency in bacteria, transiently accumulates as FolE begins to fail, stimulates the interaction between ZagA and FolE, and thereby helps to sustain folate synthesis despite declining zinc availability.
journal_name
Mol Microbioljournal_title
Molecular microbiologyauthors
Chandrangsu P,Huang X,Gaballa A,Helmann JDdoi
10.1111/mmi.14314subject
Has Abstractpub_date
2019-09-01 00:00:00pages
751-765issue
3eissn
0950-382Xissn
1365-2958journal_volume
112pub_type
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