Identification of a conserved membrane localization domain within numerous large bacterial protein toxins

Brett Geissler, Rehman Tungekar, Karla J.F. Satchell

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Vibrio cholerae is the causativeagent of the diarrheal disease cholera. Many virulence factors contribute to intestinal colonization and disease including the Multifunctional Autoprocessing RTX toxin (MARTXVc). The Rho-inactivation domain (RID) of MARTXVc is responsible for inactivating the Rho-family of small GTPases, which leads to depolymerization of the actin cytoskeleton. Based on a deletion analysis of RID to determine the minimal functional domain, we have identified a subdomain at the N terminus of RID that is homologous to the membrane targeting C1 domain of Pasteurella multocida toxin. A GFP fusion to this subdomain from RID colocalized with a plasma membrane marker when transiently expressed within HeLa cells and can be found in the membrane fraction following subcellular fractionation. This C1-like subdomain is present in multiple families of bacterial toxins, including all of the clostridial glucosyltransferase toxins and various MARTX toxins. GFP-fusions to these homologous domains are also membrane associated, indicating that this is a conserved membrane localization domain (MLD). We have identified three residues (Y23, S68, R70) as necessary for proper localization of one but not all MLDs. In addition, we found that substitution of the RID MLD with the MLDs from two different effector domains from the Vibrio vulnificus MARTX toxin restored RID activity, indicating that there is functional overlap between these MLDs. This study describes the initial recognition of a family of conserved plasma membrane-targeting domains found in multiple large bacterial toxins.

Original languageEnglish (US)
Pages (from-to)5581-5586
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number12
StatePublished - Mar 23 2010


  • Bacterial toxin
  • Multifunctional autoprocessing RTX toxin
  • PMT
  • Structural modeling
  • Vibrio cholerae

ASJC Scopus subject areas

  • General


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