Structural highlights
Function
[IPGC_SHIFL] Assists the correct folding of nascent IpaB. Once it is bound to IpaB, it binds to IpaC and impedes their premature association that would lead to their degradation in the absence of IpcG. [IPAB_SHIFL] Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. Forms a pore with IpaC, which is inserted into the host cell membrane through the Mxi/Spa apparatus, during cell contact. This pore probably allows the translocation of IpaA. IpaB has also been found to be necessary and sufficient to activate macrophage apoptosis by binding to interleukin-1 beta converting enzyme (ICE). Has also been shown to be important, along with IpaD, to block or regulate secretion through the Mxi/Spa translocon in the presence or absence of the secretion signal, respectively. Through interaction with host human MAD2L2, constitutively activates the anaphase-promoting complex APC and induces a cell cycle arrest to prevent epithelial renewal in order to promote bacterial colonization.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Type III secretion systems (TTSSs) utilized by enteropathogenic bacteria require the presence of small, acidic virulence-associated chaperones for effective host cell infection. We adopted a combination of biochemical and cellular techniques to define the chaperone binding domains (CBDs) in the translocators IpaB and IpaC associated with the chaperone IpgC from Shigella flexneri. We identified a novel CBD in IpaB and furthermore precisely mapped the boundaries of the CBDs in both translocator proteins. In IpaC a single binding domain associates with IpgC. In IpaB, we show that the binding of the newly characterized CBD is essential in maintaining the ternary arrangement of chaperone-translocator complex. This hitherto unknown function is reflected in the co-crystal structure as well, with an IpgC dimer bound to an IpaB fragment comprising both CBDs. Moreover, in the absence of this novel CBD the IpaB/IpgC complex aggregates. This dual-recognition of a domain in the protein by the chaperone in facilitating the correct chaperone-substrate organization describes a new function for the TTSS associated chaperone-substrate complexes.
Combination of two separate binding domains defines stoichiometry between type III secretion system chaperone IpgC and translocator protein IpaB.,Lokareddy RK, Lunelli M, Eilers B, Wolter V, Kolbe M J Biol Chem. 2010 Dec 17;285(51):39965-75. Epub 2010 Oct 11. PMID:20937829[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Iwai H, Kim M, Yoshikawa Y, Ashida H, Ogawa M, Fujita Y, Muller D, Kirikae T, Jackson PK, Kotani S, Sasakawa C. A bacterial effector targets Mad2L2, an APC inhibitor, to modulate host cell cycling. Cell. 2007 Aug 24;130(4):611-23. PMID:17719540 doi:10.1016/j.cell.2007.06.043
- ↑ Thirumalai K, Kim KS, Zychlinsky A. IpaB, a Shigella flexneri invasin, colocalizes with interleukin-1 beta-converting enzyme in the cytoplasm of macrophages. Infect Immun. 1997 Feb;65(2):787-93. PMID:9009343
- ↑ Lokareddy RK, Lunelli M, Eilers B, Wolter V, Kolbe M. Combination of two separate binding domains defines stoichiometry between type III secretion system chaperone IpgC and translocator protein IpaB. J Biol Chem. 2010 Dec 17;285(51):39965-75. Epub 2010 Oct 11. PMID:20937829 doi:10.1074/jbc.M110.135616
