4cc4

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Complex of InlC of Listeria monocytogenes and human Tuba C-terminal SH3 domainComplex of InlC of Listeria monocytogenes and human Tuba C-terminal SH3 domain

Structural highlights

4cc4 is a 6 chain structure with sequence from Homo sapiens and Listeria monocytogenes EGD-e. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[INLC_LISMG] A virulence enhancer that has at least 2 dissociable functions in infection; it impairs translocation of host transcription factor NF-kappa-B to the nucleus and antagonizes the function of the Tuba dynamin-binding protein, promoting bacterial spreading (PubMed:20855622, PubMed:19767742, PubMed:24332715). Perturbs the morphology of host cell junctions by impairing host DNMBP (Tuba) and WASL interaction, altering cortical tension at the cell junctions and allowing bacteria to more efficiently form bacteria-filled cell protrusions which promote bacterial spreading within infected host tissue (PubMed:19767742, PubMed:24332715). Down-regulates the host inflammation response usually induced by Listeria infection. Interacts with host I-kappa-B kinase alpha (IKKA, CHUK), which prevents IKKA from phosphorylating NF-kappa-B inhibitor alpha (IKBA, NFKBIA) and thus delays degradation of phospho-IKBA. Translocation of host transcription factor p65 (a subunit of NF-kappa-B, RELA) into the nucleus is impaired, which prevents activation of NF-KB-regulated genes (PubMed:20855622). Recognized by serum from healthy humans exposed to L.monocytogenes as well from patients who have recovered from listeriosis (PubMed:9284184).[1] [2] [3] [4]

References

  1. Rajabian T, Gavicherla B, Heisig M, Muller-Altrock S, Goebel W, Gray-Owen SD, Ireton K. The bacterial virulence factor InlC perturbs apical cell junctions and promotes cell-to-cell spread of Listeria. Nat Cell Biol. 2009 Oct;11(10):1212-8. doi: 10.1038/ncb1964. Epub 2009 Sep 20. PMID:19767742 doi:http://dx.doi.org/10.1038/ncb1964
  2. Gouin E, Adib-Conquy M, Balestrino D, Nahori MA, Villiers V, Colland F, Dramsi S, Dussurget O, Cossart P. The Listeria monocytogenes InlC protein interferes with innate immune responses by targeting the I{kappa}B kinase subunit IKK{alpha}. Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17333-8. doi:, 10.1073/pnas.1007765107. Epub 2010 Sep 20. PMID:20855622 doi:http://dx.doi.org/10.1073/pnas.1007765107
  3. Polle L, Rigano LA, Julian R, Ireton K, Schubert WD. Structural Details of Human Tuba Recruitment by InlC of Listeria monocytogenes Elucidate Bacterial Cell-Cell Spreading. Structure. 2013 Dec 10. pii: S0969-2126(13)00429-2. doi:, 10.1016/j.str.2013.10.017. PMID:24332715 doi:http://dx.doi.org/10.1016/j.str.2013.10.017
  4. Grenningloh R, Darji A, Wehland J, Chakraborty T, Weiss S. Listeriolysin and IrpA are major protein targets of the human humoral response against Listeria monocytogenes. Infect Immun. 1997 Sep;65(9):3976-80. doi: 10.1128/iai.65.9.3976-3980.1997. PMID:9284184 doi:http://dx.doi.org/10.1128/iai.65.9.3976-3980.1997

4cc4, resolution 2.60Å

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