Structural basis for subversion of host cell actin cytoskeleton during Salmonella infection
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Structural basis for subversion of host cell actin cytoskeleton during Salmonella infection. / Yuan, Biao; Scholz, Jonas; Wald, Jiri; Thuenauer, Roland; Hennell James, Rory; Ellenberg, Irina; Windhorst, Sabine; Faix, Jan; Marlovits, Thomas C.
In: SCI ADV, Vol. 9, No. 49, 08.12.2023, p. eadj5777.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Structural basis for subversion of host cell actin cytoskeleton during Salmonella infection
AU - Yuan, Biao
AU - Scholz, Jonas
AU - Wald, Jiri
AU - Thuenauer, Roland
AU - Hennell James, Rory
AU - Ellenberg, Irina
AU - Windhorst, Sabine
AU - Faix, Jan
AU - Marlovits, Thomas C
PY - 2023/12/8
Y1 - 2023/12/8
N2 - Secreted bacterial type III secretion system (T3SS) proteins are essential for successful infection by many human pathogens. Both T3SS translocator SipC and effector SipA are critical for Salmonella infection by subversion of the host cell cytoskeleton, but the precise molecular interplay between them remains unknown. Here, using cryo-electron microscopy, we show that SipA binds along the F-actin grooves with a unique binding pattern. SipA stabilizes F-actin through charged interface residues and appears to prevent inorganic phosphate release through closure of the "back door" of adenosine 5'-triphosphate pocket. We also show that SipC enhances the binding of SipA to F-actin, thus demonstrating that a sequential presence of T3SS proteins in host cells is associated with a sequence of infection events-starting with actin nucleation, filament growth, and stabilization. Together, our data explain the coordinated interplay of a precisely tuned and highly effective mechanism during Salmonella infection and provide a blueprint for interfering with Salmonella effectors acting on actin.
AB - Secreted bacterial type III secretion system (T3SS) proteins are essential for successful infection by many human pathogens. Both T3SS translocator SipC and effector SipA are critical for Salmonella infection by subversion of the host cell cytoskeleton, but the precise molecular interplay between them remains unknown. Here, using cryo-electron microscopy, we show that SipA binds along the F-actin grooves with a unique binding pattern. SipA stabilizes F-actin through charged interface residues and appears to prevent inorganic phosphate release through closure of the "back door" of adenosine 5'-triphosphate pocket. We also show that SipC enhances the binding of SipA to F-actin, thus demonstrating that a sequential presence of T3SS proteins in host cells is associated with a sequence of infection events-starting with actin nucleation, filament growth, and stabilization. Together, our data explain the coordinated interplay of a precisely tuned and highly effective mechanism during Salmonella infection and provide a blueprint for interfering with Salmonella effectors acting on actin.
KW - Humans
KW - Actins/metabolism
KW - Cryoelectron Microscopy
KW - Bacterial Proteins/metabolism
KW - Actin Cytoskeleton/metabolism
KW - Salmonella Infections
U2 - 10.1126/sciadv.adj5777
DO - 10.1126/sciadv.adj5777
M3 - SCORING: Journal article
C2 - 38064550
VL - 9
SP - eadj5777
JO - SCI ADV
JF - SCI ADV
SN - 2375-2548
IS - 49
ER -