6sus

Crystal structure of RTX domain blocks IV and V of adenylate cyclase toxin from Bordetella pertussis

spinqualitylabelsall models 6sus, resolution 1.76Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6sus is a 1 chain structure with sequence from Bordetella pertussis Tohama I. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.76Å Ligands: CA, EDO, GOL, NO3, PGE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CYAA_BORPE This adenylate cyclase belongs to a special class of bacterial toxin. It causes whooping cough by acting on mammalian cells by elevating cAMP-concentration and thus disrupts normal cell function. Publication Abstract from PubMed Repeats-in-Toxin (RTX) proteins of Gram-negative bacteria are excreted through the type I secretion system (T1SS) that recognizes non-cleavable C-terminal secretion signals. These are preceded by arrays of glycine and aspartate-rich nonapeptide repeats grouped by four to eight beta strands into blocks that fold into calcium-binding parallel beta-roll structures. The beta-rolls are interspersed by linkers of variable length and sequence and the organization of multiple RTX repeat blocks within large RTX domains remains unknown. Here we examined the structure and function of the RTX domain of Bordetella pertussis adenylate cyclase toxin (CyaA) that is composed of five beta-roll RTX blocks. We show that the non-folded RTX repeats maintain the stability of the CyaA polypeptide in the Ca(2+)-depleted bacterial cytosol and thereby enable its efficient translocation through the T1SS apparatus. The efficacy of secretion of truncated CyaA constructs was dictated by the number of retained RTX repeat blocks and depended on the presence of extracellular Ca(2+) ions. We further describe the crystal structure of the RTX blocks IV-V of CyaA (CyaA1372-1681) that consists of a contiguous assembly of two beta-rolls that differs substantially from the arrangement of the RTX blocks observed in RTX lipases or other RTX proteins. These results provide a novel structural insight into the architecture of the RTX domains of large RTX proteins and support the "push-ratchet" mechanism of the T1SS-mediated secretion of very large RTX proteins. Continuous Assembly of beta-Roll Structures Is Implicated in the Type I-Dependent Secretion of Large Repeat-in-Toxins (RTX) Proteins.,Motlova L, Klimova N, Fiser R, Sebo P, Bumba L J Mol Biol. 2020 Aug 27. pii: S0022-2836(20)30514-3. doi:, 10.1016/j.jmb.2020.08.020. PMID:32860773 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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