Abstract
Pathogenic Yersinia species evade host immune systems through the injection of Yersinia outer proteins (Yops) into phagocytic cells. One Yop, YopO, also known as YpkA, induces actin-filament disruption, impairing phagocytosis. Here we describe the X-ray structure of Yersinia enterocolitica YopO in complex with actin, which reveals that YopO binds to an actin monomer in a manner that blocks polymerization yet allows the bound actin to interact with host actin-regulating proteins. SILAC-MS and biochemical analyses confirm that actin-polymerization regulators such as VASP, EVL, WASP, gelsolin and the formin diaphanous 1 are directly sequestered and phosphorylated by YopO through formation of ternary complexes with actin. This leads to a model in which YopO at the membrane sequesters actin from polymerization while using the bound actin as bait to recruit, phosphorylate and misregulate host actin-regulating proteins to disrupt phagocytosis.
| Original language | English |
|---|---|
| Pages (from-to) | 248-255 |
| Number of pages | 8 |
| Journal | Nature Structural and Molecular Biology |
| Volume | 22 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 6 2015 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Structural Biology
- Molecular Biology
- Medicine(all)
Cite this
Yersinia effector YopO uses actin as bait to phosphorylate proteins that regulate actin polymerization. / Lee, Wei Lin; Grimes, Jonathan M.; Robinson, Robert C.
In: Nature Structural and Molecular Biology, Vol. 22, No. 3, 06.03.2015, p. 248-255.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Yersinia effector YopO uses actin as bait to phosphorylate proteins that regulate actin polymerization
AU - Lee, Wei Lin
AU - Grimes, Jonathan M.
AU - Robinson, Robert C.
PY - 2015/3/6
Y1 - 2015/3/6
N2 - Pathogenic Yersinia species evade host immune systems through the injection of Yersinia outer proteins (Yops) into phagocytic cells. One Yop, YopO, also known as YpkA, induces actin-filament disruption, impairing phagocytosis. Here we describe the X-ray structure of Yersinia enterocolitica YopO in complex with actin, which reveals that YopO binds to an actin monomer in a manner that blocks polymerization yet allows the bound actin to interact with host actin-regulating proteins. SILAC-MS and biochemical analyses confirm that actin-polymerization regulators such as VASP, EVL, WASP, gelsolin and the formin diaphanous 1 are directly sequestered and phosphorylated by YopO through formation of ternary complexes with actin. This leads to a model in which YopO at the membrane sequesters actin from polymerization while using the bound actin as bait to recruit, phosphorylate and misregulate host actin-regulating proteins to disrupt phagocytosis.
AB - Pathogenic Yersinia species evade host immune systems through the injection of Yersinia outer proteins (Yops) into phagocytic cells. One Yop, YopO, also known as YpkA, induces actin-filament disruption, impairing phagocytosis. Here we describe the X-ray structure of Yersinia enterocolitica YopO in complex with actin, which reveals that YopO binds to an actin monomer in a manner that blocks polymerization yet allows the bound actin to interact with host actin-regulating proteins. SILAC-MS and biochemical analyses confirm that actin-polymerization regulators such as VASP, EVL, WASP, gelsolin and the formin diaphanous 1 are directly sequestered and phosphorylated by YopO through formation of ternary complexes with actin. This leads to a model in which YopO at the membrane sequesters actin from polymerization while using the bound actin as bait to recruit, phosphorylate and misregulate host actin-regulating proteins to disrupt phagocytosis.
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UR - http://www.scopus.com/inward/citedby.url?scp=84924101878&partnerID=8YFLogxK
U2 - 10.1038/nsmb.2964
DO - 10.1038/nsmb.2964
M3 - Article
C2 - 25664724
AN - SCOPUS:84924101878
VL - 22
SP - 248
EP - 255
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
SN - 1545-9993
IS - 3
ER -