Structural highlights
Function
[SPAK_SALTY] Involved in a secretory pathway responsible for the surface presentation of determinants needed for the entry of Salmonella species into mammalian cells. Chaperone specialized in the storage of effectors within the bacterial cytoplasm, maintaining them in a secretion-competent state, and allowing their immediate delivery to target cells upon contact of the bacterium with the host cells. Has been shown to chaperone SopA, SopE, SopE2 and SipA.[1] [2] [SIPA_SALTY] Actin-binding protein that interferes with host cell actin cytoskeleton. It stimulates actin polymerization and counteracts F-actin destabilizing proteins. Potentiates SipC activity; both are required for an efficient bacterial internalization. In vitro, forms a complex with host cell protein T-plastin increasing actin bundling. It inhibits ADF/cofilin-directed depolymerization both by preventing binding of ADF and cofilin and by displacing them from F-actin. Also protects F-actin from gelsolin-directed severing and reanneals gelsolin-severed F-actin fragments.[3] [4]
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
Salmonella invasion protein A (SipA) is translocated into host cells by a type III secretion system (T3SS) and comprises two regions: one domain binds its cognate type III secretion chaperone, InvB, in the bacterium to facilitate translocation, while a second domain functions in the host cell, contributing to bacterial uptake by polymerizing actin. We present here the crystal structures of the SipA chaperone binding domain (CBD) alone and in complex with InvB. The SipA CBD is found to consist of a nonglobular polypeptide as well as a large globular domain, both of which are necessary for binding to InvB. We also identify a structural motif that may direct virulence factors to their cognate chaperones in a diverse range of pathogenic bacteria. Disruption of this structural motif leads to a destabilization of several chaperone-substrate complexes from different species, as well as an impairment of secretion in Salmonella.
A common structural motif in the binding of virulence factors to bacterial secretion chaperones.,Lilic M, Vujanac M, Stebbins CE Mol Cell. 2006 Mar 3;21(5):653-64. PMID:16507363[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Higashide W, Zhou D. The first 45 amino acids of SopA are necessary for InvB binding and SPI-1 secretion. J Bacteriol. 2006 Apr;188(7):2411-20. PMID:16547027 doi:http://dx.doi.org/10.1128/JB.188.7.2411-2420.2006
- ↑ Lilic M, Vujanac M, Stebbins CE. A common structural motif in the binding of virulence factors to bacterial secretion chaperones. Mol Cell. 2006 Mar 3;21(5):653-64. PMID:16507363 doi:10.1016/j.molcel.2006.01.026
- ↑ Zhou D, Mooseker MS, Galan JE. Role of the S. typhimurium actin-binding protein SipA in bacterial internalization. Science. 1999 Mar 26;283(5410):2092-5. PMID:10092234
- ↑ McGhie EJ, Hayward RD, Koronakis V. Control of actin turnover by a salmonella invasion protein. Mol Cell. 2004 Feb 27;13(4):497-510. PMID:14992720
- ↑ Lilic M, Vujanac M, Stebbins CE. A common structural motif in the binding of virulence factors to bacterial secretion chaperones. Mol Cell. 2006 Mar 3;21(5):653-64. PMID:16507363 doi:10.1016/j.molcel.2006.01.026
