7bwt

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SopD-Rab8 complex structureSopD-Rab8 complex structure

Structural highlights

7bwt is a 2 chain structure with sequence from Homo sapiens and Salmonella enterica subsp. enterica serovar Typhimurium. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SOPD_SALTY Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. Contributes to replication in macrophages. Plays a role, cooperatively with SopB, in membrane fission and macropinosome formation during invasion.[1] [2]

Publication Abstract from PubMed

The food-borne bacterial pathogen Salmonella Typhimurium uses a type III protein secretion system to deliver multiple proteins into host cells. These secreted effectors modulate the functions of host cells and activate specific signalling cascades that result in the production of pro-inflammatory cytokines and intestinal inflammation. Some of the Salmonella-encoded effectors counteract this inflammatory response and help to preserve host homeostasis. Here, we demonstrate that the Salmonella effector protein SopD, which is required for pathogenesis, functions to both activate and inhibit the inflammatory response by targeting the Rab8 GTPase, which is a negative regulator of inflammation. We show that SopD has GTPase-activating protein activity for Rab8 and, therefore, inhibits this GTPase and stimulates inflammation. We also show that SopD activates Rab8 by displacing it from its cognate guanosine dissociation inhibitor, resulting in the stimulation of a signalling cascade that suppresses inflammation. We solved the crystal structure of SopD in association with Rab8 to a resolution of 2.3 A, which reveals a unique contact interface that underlies these complex interactions. These findings show the remarkable evolution of a bacterial effector protein to exert both agonistic and antagonistic activities towards the same host cellular target to modulate the inflammatory response.

The Salmonella effector protein SopD targets Rab8 to positively and negatively modulate the inflammatory response.,Lian H, Jiang K, Tong M, Chen Z, Liu X, Galan JE, Gao X Nat Microbiol. 2021 May;6(5):658-671. doi: 10.1038/s41564-021-00866-3. Epub 2021 , Feb 18. PMID:33603205[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Jiang X, Rossanese OW, Brown NF, Kujat-Choy S, Galan JE, Finlay BB, Brumell JH. The related effector proteins SopD and SopD2 from Salmonella enterica serovar Typhimurium contribute to virulence during systemic infection of mice. Mol Microbiol. 2004 Dec;54(5):1186-98. PMID:15554961 doi:http://dx.doi.org/10.1111/j.1365-2958.2004.04344.x
  2. Bakowski MA, Cirulis JT, Brown NF, Finlay BB, Brumell JH. SopD acts cooperatively with SopB during Salmonella enterica serovar Typhimurium invasion. Cell Microbiol. 2007 Dec;9(12):2839-55. Epub 2007 Aug 13. PMID:17696999 doi:http://dx.doi.org/10.1111/j.1462-5822.2007.01000.x
  3. Lian H, Jiang K, Tong M, Chen Z, Liu X, Galán JE, Gao X. The Salmonella effector protein SopD targets Rab8 to positively and negatively modulate the inflammatory response. Nat Microbiol. 2021 May;6(5):658-671. PMID:33603205 doi:10.1038/s41564-021-00866-3

7bwt, resolution 2.30Å

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