6TAO

The cytotoxin MakE from Vibrio cholerae

Summary for 6TAO

• Entry DOI: 10.2210/pdb6tao/pdb
• Descriptor: Non-hemolytic enterotoxin lytic component L1, NICKEL (II) ION, SULFATE ION, ... (4 entities in total)
• Functional Keywords: cytotoxin cholera, toxin
• Biological source: Vibrio cholerae
• Total number of polymer chains: 2
• Total formula weight: 78746.01

Authors

Persson, K.,Nagampalli, R.,Heidler, T.,Wai, S.N. (deposition date: 2019-10-30, release date: 2020-11-18, Last modification date: 2024-06-19)

Primary citation

Nadeem, A.,Nagampalli, R.,Toh, E.,Alam, A.,Myint, S.L.,Heidler, T.V.,Dongre, M.,Zlatkov, N.,Pace, H.,Bano, F.,Sjostedt, A.,Bally, M.,Uhlin, B.E.,Wai, S.N.,Persson, K.
A tripartite cytolytic toxin formed by Vibrio cholerae proteins with flagellum-facilitated secretion.
Proc.Natl.Acad.Sci.USA, 118:-, 2021

PubMed Abstract: The protein MakA was discovered as a motility-associated secreted toxin from 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 , 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 resulted in toxicity toward 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 Bioinformatic analyses revealed that the gene cluster is present as a genomic island in the vast majority of sequenced genomes of and the fish pathogen 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.

PubMed: 34799450
DOI: 10.1073/pnas.2111418118

Experimental method

X-RAY DIFFRACTION (1.98 Å)