Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 426, Issue 15, Pages 2800-2812Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2014.05.021
Keywords
bacterial pathogenesis; carbohydrate; crystallography; cytolysin; pore-forming toxin
Categories
Funding
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R15 AI101977]
- National Institutes of Health [R24 GM098791]
- Offices of Biological and Environmental Research and of Basic Energy Sciences of the US Department of Energy
- National Center for Research Resources [P41RR012408]
- National Institute of General Medical Sciences of the National Institutes of Health [P41GM103473]
Ask authors/readers for more resources
Pore-forming toxins (PFTs) are 6 class of pathogen-secreted molecules that oligomerize to form transmembrane channels in cellular membranes. Determining the mechanism for how PFTs bind membranes is important in understanding their role in disease and for developing possible ways to block their action. Vibrio vulnificus, an aquatic pathogen responsible for severe food poisoning and septicemia in humans, secretes a PFT called V. vulnificus hemolysin (VVH), which contains a single C-terminal targeting domain predicted to resemble a beta-trefoil lectin fold. In order to understand the selectivity of the lectin for glycan motifs, we expressed the isolated VVH beta-trefoil domain and used glycan-chip screening to identify that VVH displays a preference for terminal galactosyl groups including N-acetyl-D-galactosamine and N-acetyl-D-lactosamine. The X-ray crystal structure of the VVH lectin domain solved to 2.0 angstrom resolution reveals a heptameric ring arrangement similar to the oligonneric form of the related, but inactive, lectin from Vibrio cholerae cytolysin. Structures bound to glycerol, N-acetyl-D-galactosamine, and N-acetyl-D-lactosamine outline a common and versatile mode of recognition allowing VVH to target a wide variety of cell-surface ligands. Sequence analysis in light of our structural and functional data suggests that VVH may represent an earlier step in the evolution of Vibrio PFTs. (C) 2014 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available