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Summary
Glutathione (
GSH
) protects cells against oxidative injury and maintains a range of vital functions across all branches of life. Despite recent advances in our understanding of the transport mechanisms responsible for maintaining the spatiotemporal homeostasis of
GSH
and its conjugates in eukaryotes and Gram‐negative bacteria, the molecular and structural basis of
GSH
import into Gram‐positive bacteria has remained largely uncharacterized. Here, we employ genetic, biochemical and structural studies to investigate a possible glutathione import axis in
S
treptococcus mutans
, an organism that has hitherto served as a model system. We show that
GshT
, a type 3 solute binding protein, displays physiologically relevant affinity for
GSH
and glutathione disulfide (
GSSG
). The crystal structure of
GshT
in complex with
GSSG
reveals a collapsed structure whereby the
GS
‐
I
‐leg of
GSSG
is accommodated tightly via extensive interactions contributed by the
N
‐ and
C
‐terminal lobes of
GshT
, while the
GS‐II
leg extends to the solvent. This can explain the ligand promiscuity of
GshT
in terms of binding glutathione analogues with substitutions at the cysteine‐sulfur or the glycine‐carboxylate. Finally, we show that
GshT
primes glutathione import via the
l
‐cystine
ABC
transporter
TcyBC
, a membrane permease, which had previously exclusively been associated with the transport of
l
‐cystine.
Sprache
Englisch
Identifikatoren
ISSN: 0950-382X
eISSN: 1365-2958
DOI: 10.1111/mmi.12274
Titel-ID: cdi_crossref_primary_10_1111_mmi_12274
Format
–
Weiterführende Literatur
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