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PDBsum entry 6mw4
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Signaling protein
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PDB id
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6mw4
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References listed in PDB file
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Key reference
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Title
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The cspc pseudoprotease regulates germination of clostridioides difficile spores in response to multiple environmental signals.
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Authors
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A.E.Rohlfing,
B.E.Eckenroth,
E.R.Forster,
Y.Kevorkian,
M.L.Donnelly,
H.Benito de la puebla,
S.Doublié,
A.Shen.
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Ref.
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PLoS Genet, 2019,
15,
e1008224.
[DOI no: ]
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PubMed id
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Abstract
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The gastrointestinal pathogen, Clostridioides difficile, initiates infection
when its metabolically dormant spore form germinates in the mammalian gut. While
most spore-forming bacteria use transmembrane germinant receptors to sense
nutrient germinants, C. difficile is thought to use the soluble pseudoprotease,
CspC, to detect bile acid germinants. To gain insight into CspC's unique
mechanism of action, we solved its crystal structure. Guided by this structure,
we identified CspC mutations that confer either hypo- or hyper-sensitivity to
bile acid germinant. Surprisingly, hyper-sensitive CspC variants exhibited bile
acid-independent germination as well as increased sensitivity to amino acid
and/or calcium co-germinants. Since mutations in specific residues altered
CspC's responsiveness to these different signals, CspC plays a critical role in
regulating C. difficile spore germination in response to multiple environmental
signals. Taken together, these studies implicate CspC as being intimately
involved in the detection of distinct classes of co-germinants in addition to
bile acids and thus raises the possibility that CspC functions as a signaling
node rather than a ligand-binding receptor.
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