# SHIGELLA TOXIN:  STRUCTURE & FUNCTION RELATIONSHIPS

> **NIH NIH R01** · TUFTS MEDICAL CENTER · 1989 · $138,374

## Abstract

Shigellosis is a world wide disease producing significant morbidity
and in developing countries, a leading cause of diarrheal disease
mortality.  Pathogenesis involves invasion of colonic epithelial
cells.  A protein toxin is now believed to be a second improtant
virulence factor.  The same or very similar toxin is produced by
non-invasive enteropathogenic E. coli and other organisms.  The
toxin molecule consists of one A chain and 5 B chains.  A
functional role of the B chains is to mediate toxin binding to the
eukaryotic cell surface.  A glycolipid has been shown to be a toxin
receptor and a glycoprotein receptor with a different sugar
specificity (GlcNAc3) is also involved.

This proposal is designed to study basic structure-function
relationships of the toxin B chain.  Particular emphasis will be
placed on the structrual location of the two binding domains and
on their biological roles in mediating the biological activities of
the toxin.  Thorugh the use of the glycoprotein receptor analogue,
chitotetraose, direct evidence for the two binding domains will
first be documented.  Since the B chains exist in multimer form in
the individual monomers and/or regions of B to B interaction.  A
chemical cross-linker will be used to determine the inter or intra-
chain location of the binding domains.  By intraluminal injections
of toxin with soluble receptor analogues the role of the two
receptors in mediating fluid secretion in rabbits wil be analyzed.
Immunization of rabbits with synthetic peptides derived from the
B chain amino acid sequence will lead to antibodies that will be
tested for their ability to neutralized the biological activity of
toxin.  Information from this study will be useful for the future
design of safe and effective toxin vaccines.  Finally by both
specific chemical modification of the B chain and by the study of
B chain mutants information on the location of amino acids
involved in important B chain functions will be determined.

## Key facts

- **NIH application ID:** 3129923
- **Project number:** 5R01AI020325-06
- **Recipient organization:** TUFTS MEDICAL CENTER
- **SAM.gov UEI:** MY2ERHGDV956
- **Principal Investigator:** ARTHUR M. DONOHUE-ROLFE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $138,374
- **Award type:** 5
- **Project period:** 1984-04-01 → 1990-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129923

## Citation

> US National Institutes of Health, RePORTER application 3129923, SHIGELLA TOXIN:  STRUCTURE & FUNCTION RELATIONSHIPS (5R01AI020325-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129923. Licensed CC0.

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