+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Presence of actin binding motif in VgrG-1 toxin of Vibrio cholerae reveals the molecular mechanism of actin cross-linking



Presence of actin binding motif in VgrG-1 toxin of Vibrio cholerae reveals the molecular mechanism of actin cross-linking



International Journal of Biological Macromolecules 133: 775-785



Type VI secretion systems (T6SS) plays a crucial role in Vibrio cholerae mediated pathogenicity. Tip of T6SS is homologous to gp27/gp5 complex or tail spike of T4 bacteriophage. VgrG-1 of V. cholerae T6SS is unusual among other VgrG because its effector domain is trans-located into the cytosol of eukaryotic cells with an additional actin cross-linking domain (ACD) at its C terminal end. ACD of VgrG-1 (VgrG-1-ACD) causes T6SS dependent host cell cytotoxicity through actin cytoskeleton disruption to prevent bacterial engulfment by macrophages. ACD mediated actin cross-linking promotes survival of the bacteria in the small intestine of humans, along with other virulence factors; establishes successful infection with the onset of diarrhoea in humans. Our studies demonstrated VgrG-1-ACD can bind to actin besides actin cross-linking activity. Computational analysis of ACD revealed the presence of actin binding motif (ABM). Mutations in ABM lead to loss of actin binding in vitro. VgrG-1-ACD having the mutated ABM cannot cross-link actin efficiently in vitro and manifests less actin cytoskeleton disruption when transfected in HeLa cells.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 066706926

Download citation: RISBibTeXText

PMID: 31002899

DOI: 10.1016/j.ijbiomac.2019.04.026


Related references

The Actin cross-linking domain of the Vibrio cholerae RTX toxin directly catalyzes the covalent cross-linking of actin. Journal of Biological Chemistry 281(43): 32366-32374, 2006

In vivo covalent cross-linking of cellular actin by the Vibrio cholerae RTX toxin. Embo Journal 19(20): 5315-5323, 2000

RTX toxin actin cross-linking activity in clinical and environmental isolates of Vibrio cholerae. Journal of Clinical Microbiology 45(7): 2289-2292, 2007

Characterization of the enzymatic activity of the actin cross-linking domain from the Vibrio cholerae MARTX Vc toxin. Journal of Biological Chemistry 283(1): 445-452, 2008

Genetic determination of essential residues of the Vibrio cholerae actin cross-linking domain reveals functional similarity with glutamine synthetases. Molecular Microbiology 73(5): 858-868, 2009

Actin Cross-Linking Toxin Is a Universal Inhibitor of Tandem-Organized and Oligomeric G-Actin Binding Proteins. Current Biology 28(10): 1536-1547.E9, 2018

Chemical cross-linking of actin mutants and the actin binding domain of alpha-actin. Molecular Biology of the Cell 6(Suppl. ): 19A, 1995

Crystal structure of the VgrG1 actin cross-linking domain of the Vibrio cholerae type VI secretion system. Journal of Biological Chemistry 287(45): 38190-9, 2012

In vivo actin cross-linking induced by Vibrio cholerae type VI secretion system is associated with intestinal inflammation. Proceedings of the National Academy of Sciences of the United States of America 107(9): 4365-4370, 2010

Identification of a domain within the multifunctional Vibrio cholerae RTX toxin that covalently cross-links actin. Proceedings of the National Academy of Sciences of the United States of America 101(26): 9798-9803, 2004

Connecting actin monomers by iso-peptide bond is a toxicity mechanism of the Vibrio cholerae MARTX toxin. Proceedings of the National Academy of Sciences of the United States of America 105(47): 18537-18542, 2008

The interaction of plectin with actin: evidence for cross-linking of actin filaments by dimerization of the actin-binding domain of plectin. Journal of Cell Science 114(Pt 11): 2065-2076, 2001

Actin-actin contact: chemical cross-linking between actin and the 2.6-kDa peptide from subdomain 4 of actin. Journal of Biochemistry 118(6): 1232-1238, 1995

The effect of the 540-kilodalton actin cross-linking protein, actin-binding protein, on the mechanical properties of F-actin. Journal of Biological Chemistry 261(17): 7615-7620, 1986

Further characterization of a conserved actin-binding 27-kDa fragment of actinogelin and a-actinins and mapping of their binding sites on the actin molecule by chemical cross-linking. The Journal of Biological Chemistry 262: 17-23, 1987