ACTIN-DIRECTED TOXIN. ACD toxin-produced actin oligomers poison formin-controlled actin polymerization.

Article Details

Citation

Heisler DB, Kudryashova E, Grinevich DO, Suarez C, Winkelman JD, Birukov KG, Kotha SR, Parinandi NL, Vavylonis D, Kovar DR, Kudryashov DS

ACTIN-DIRECTED TOXIN. ACD toxin-produced actin oligomers poison formin-controlled actin polymerization.

Science. 2015 Jul 31;349(6247):535-9. doi: 10.1126/science.aab4090.

PubMed ID
26228148 [ View in PubMed
]
Abstract

The actin cross-linking domain (ACD) is an actin-specific toxin produced by several pathogens, including life-threatening spp. of Vibrio cholerae, Vibrio vulnificus, and Aeromonas hydrophila. Actin cross-linking by ACD is thought to lead to slow cytoskeleton failure owing to a gradual sequestration of actin in the form of nonfunctional oligomers. Here, we found that ACD converted cytoplasmic actin into highly toxic oligomers that potently "poisoned" the ability of major actin assembly proteins, formins, to sustain actin polymerization. Thus, ACD can target the most abundant cellular protein by using actin oligomers as secondary toxins to efficiently subvert cellular functions of actin while functioning at very low doses.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Actin, alpha skeletal muscleP68133Details
Actin, cytoplasmic 1P60709Details
Actin, cytoplasmic 2P63261Details
Actin, aortic smooth muscleP62736Details