4ow6

Crystal structure of Diphtheria Toxin at acidic pH

spinqualitylabelsall models 4ow6, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ow6 is a 2 chain structure with sequence from Corynebacterium diphtheriae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Activity: NAD(+)--diphthamide ADP-ribosyltransferase, with EC number 2.4.2.36 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Diphtheria toxin (DT), the etiological agent of the homonymous disease, like other bacterial toxins has to undergo a dramatic structural change in order to be internalized into the cytosol, where it finally performs its function. The molecular mechanism of toxin transit across the membrane is ill-known, but available experimental evidences indicate that one of the three domains of the toxin, called domain T, inserts into the lipid bilayer, so favouring the translocation of the catalytic domain C. This process is driven by the acidic pH of the endosomal lumen. Here, we describe the crystal structure of DT grown at acidic pH in the presence of bicelles. We were unable to freeze the moment of DT insertion into the lipid bilayer, but our crystal structure indicates that the low pH causes the unfolding of alpha-helices TH2, TH3 and TH4. This event gives rise to the exposure of a hydrophobic surface that includes alpha-helices TH5, TH8 and the loop region connecting alpha-helices TH8 and TH9. Their exposure is probably favored by the presence of lipid bilayers in the crystallization solution, and they appear to be ready to insert into the membrane. This article is protected by copyright. All rights reserved. Diphtheria Toxin conformational switching at acidic pH.,Leka O, Vallese F, Pirazzini M, Berto P, Montecucco C, Zanotti G FEBS J. 2014 Mar 15. doi: 10.1111/febs.12783. PMID:24628974 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Diphtheria toxin

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