6t8d | pdb_00006t8d

The cytotoxin MakB from Vibrio cholerae

spinqualitylabelsall models 6t8d, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6t8d is a 1 chain structure with sequence from Vibch. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SO4 Gene: VC_A0882 (VIBCH) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The protein MakA was discovered as a motility-associated secreted toxin from Vibrio cholerae Here, we show that MakA is part of a gene cluster encoding four additional proteins: MakB, MakC, MakD, and MakE. MakA, MakB, and MakE were readily detected in culture supernatants of wild-type V. cholerae, whereas secretion was very much reduced from a flagellum-deficient mutant. Crystal structures of MakA, MakB, and MakE revealed a structural relationship to a superfamily of bacterial pore-forming toxins. Expression of MakA/B/E in Escherichia coli resulted in toxicity toward Caenorhabditis elegans used as a predatory model organism. None of these Mak proteins alone or in pairwise combinations were cytolytic, but an equimolar mixture of MakA, MakB, and MakE acted as a tripartite cytolytic toxin in vitro, causing lysis of erythrocytes and cytotoxicity on cultured human colon carcinoma cells. Formation of oligomeric complexes on liposomes was observed by electron microscopy. Oligomer interaction with membranes was initiated by MakA membrane binding followed by MakB and MakE joining the assembly of a pore structure. A predicted membrane insertion domain of MakA was shown by site-directed mutagenesis to be essential for toxicity toward C. elegans Bioinformatic analyses revealed that the makCDBAE gene cluster is present as a genomic island in the vast majority of sequenced genomes of V. cholerae and the fish pathogen Vibrio anguillarum We suggest that the hitherto-unrecognized cytolytic MakA/B/E toxin can contribute to Vibrionaceae fitness and virulence potential in different host environments and organisms. A tripartite cytolytic toxin formed by Vibrio cholerae proteins with flagellum-facilitated secretion.,Nadeem A, Nagampalli R, Toh E, Alam A, Myint SL, Heidler TV, Dongre M, Zlatkov N, Pace H, Bano F, Sjostedt A, Bally M, Uhlin BE, Wai SN, Persson K Proc Natl Acad Sci U S A. 2021 Nov 23;118(47). pii: 2111418118. doi:, 10.1073/pnas.2111418118. PMID:34799450 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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