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Title: A structural comparison of Listeria monocytogenes protein chaperones PrsA1 and PrsA2 reveals molecular features required for virulence

Journal Article · · Molecular Microbiology
DOI:https://doi.org/10.1111/mmi.13367· OSTI ID:1438861

Listeria monocytogenes is a Gram-positive environmental bacterium that lives within soil but transitions into a pathogen upon contact with a mammalian host. The transition of L. monocytogenes from soil dweller to cytosolic pathogen is dependent upon secreted virulence factors that mediate cell invasion and intracellular growth. PrsA1 and PrsA2 are secreted bacterial lipoprotein chaperones that contribute to the folding of proteins translocated across the bacterial membrane; PrsA2 is required for L. monocytogenes virulence, whereas the function of PrsA1 remains to be determined. We have solved an X-ray crystal structure of PrsA1 and have used this model to guide comparison structure-based mutagenesis studies with PrsA2. Targeted mutagenesis of PrsA2 demonstrates that oligomerization of PrsA2 as well as molecular features of the foldase domain are required for protein secretion and virulence, whereas a functional role was uncovered for PrsA1 in bacterial resistance to alcohol. Interestingly, PrsA2 membrane localization is not required for all PrsA2-dependent activities, suggesting that the lipoprotein retains function when released from the bacterial cell. Finally, PrsA chaperones are thus multifaceted proteins with distinct domains adapted to accommodate the functional needs of a diverse array of secreted substrates.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
USDOE Office of Science (SC); National Institutes of Health (NIH)
Grant/Contract Number:
AC02-06CH11357; 085P1000817; R01 AI083241; AI083241-03S1
OSTI ID:
1438861
Journal Information:
Molecular Microbiology, Vol. 101, Issue 1; ISSN 0950-382X
Publisher:
WileyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 12 works
Citation information provided by
Web of Science

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Cited By (3)

NmPin from the marine thaumarchaeote Nitrosopumilus maritimus is an active membrane associated prolyl isomerase journal June 2016
Identification and optimization of PrsA in Bacillus subtilis for improved yield of amylase journal September 2019
The conserved mosaic prophage protein paratox inhibits the natural competence regulator ComR in Streptococcus journal November 2018