3r9v

Cocrystal Structure of Proteolytically Truncated Form of IpaD from Shigella flexneri Bound to Deoxycholate

spinqualitylabelsall models 3r9v, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3r9v is a 2 chain structure with sequence from "shigella_paradysenteriae"_weldin_1927 "shigella paradysenteriae" weldin 1927. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: DXC, GOL Gene: ipaD, CP0126 ("Shigella paradysenteriae" Weldin 1927) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [IPAD_SHIFL] Required for bacterial invasion of host cells. Controls IpaB and IpaC secretion, and the efficiency with which they are physically inserted into target cell membranes. These proteins are exported via TTSS to form a pore in the host membrane that allows the translocation of the other effectors into the host cytoplasm. Along with IpaB, is essential for both blocking secretion through the Mxi/Spa translocon in the absence of a secretion-inducing signal, and for controlling the level of secretion in the presence of this signal. Publication Abstract from PubMed Type III secretion (TTS) is an essential virulence factor for Shigella flexneri, the causative agent of shigellosis. The Shigella TTS apparatus (TTSA) is an elegant nanomachine that is composed of a basal body, an external needle to deliver effectors into human cells, and a needle tip complex that controls secretion activation. IpaD is at the tip of the nascent TTSA needle where it controls the first step of TTS activation. The bile salt deoxycholate (DOC) binds to IpaD to induce recruitment of the translocator protein IpaB into the maturing tip complex. We recently used spectroscopic analyses to show that IpaD undergoes a structural rearrangement that accompanies binding to DOC. Here, we report a crystal structure of IpaD with DOC bound and test the importance of the residues that make up the DOC binding pocket on IpaD function. IpaD binds DOC at the interface between helices alpha3 and alpha7, with concomitant movement in the orientation of helix alpha7 relative to its position in unbound IpaD. When the IpaD residues involved in DOC binding are mutated, some are found to lead to altered invasion and secretion phenotypes. These findings suggest that adoption of a DOC bound structural state for IpaD primes the Shigella TTSA for contact with host cells. The data presented here and in the studies leading up to this work provide the foundation for developing a model of the first step in Shigella TTS activation. Identification of the bile salt binding site on IpaD from Shigella flexneri and the influence of ligand binding on IpaD structure.,Barta ML, Guragain M, Adam P, Dickenson NE, Patil M, Geisbrecht BV, Picking WL, Picking WD Proteins. 2012 Mar;80(3):935-45. PMID:22423359 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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