5b0n

Structural highlights

Function

[IPA9_SHIFL] Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein is an E3 ubiquitin ligase that interferes with host's ubiquitination pathway and modulates the acute inflammatory responses, thus facilitating bacterial colonization within the host cell. Interacts with IKBKG (NEMO) and TNIP1 (ABIN-1), an ubiquitin-binding adapter protein, which results in TNIP1-dependent 'Lys-27'-linked polyubiquitination of IKBKG. Consequently, polyubiquitinated IKBKG undergoes proteasome-dependent degradation, which perturbs NF-kappa-B activation during bacterial infection. Uses UBE2D2 (UBCH5B) as an E2 ubiquitin-conjugating enzyme.^{[1] [2] [3]}

References

1. ↑ Okuda J, Toyotome T, Kataoka N, Ohno M, Abe H, Shimura Y, Seyedarabi A, Pickersgill R, Sasakawa C. Shigella effector IpaH9.8 binds to a splicing factor U2AF(35) to modulate host immune responses. Biochem Biophys Res Commun. 2005 Jul 29;333(2):531-9. PMID:15950937 doi:10.1016/j.bbrc.2005.05.145
2. ↑ Rohde JR, Breitkreutz A, Chenal A, Sansonetti PJ, Parsot C. Type III secretion effectors of the IpaH family are E3 ubiquitin ligases. Cell Host Microbe. 2007 Mar 15;1(1):77-83. PMID:18005683 doi:10.1016/j.chom.2007.02.002
3. ↑ Ashida H, Kim M, Schmidt-Supprian M, Ma A, Ogawa M, Sasakawa C. A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO/IKKgamma to dampen the host NF-kappaB-mediated inflammatory response. Nat Cell Biol. 2010 Jan;12(1):66-73; sup pp 1-9. doi: 10.1038/ncb2006. Epub 2009 , Dec 13. PMID:20010814 doi:10.1038/ncb2006
4. ↑ Takagi K, Kim M, Sasakawa C, Mizushima T. Crystal structure of the substrate-recognition domain of the Shigella E3 ligase IpaH9.8. Acta Crystallogr F Struct Biol Commun. 2016 Apr 1;72(Pt 4):269-75. doi:, 10.1107/S2053230X16002715. Epub 2016 Mar 16. PMID:27050259 doi:http://dx.doi.org/10.1107/S2053230X16002715