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FRISC: The Faculty Research Interests Science Comparator |
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Professor of Microbiology
Immunology
Molecular Microbiology
Office: (214) 648-5930
FAX: (214) 648-5906
Email: leidel@mednet.swmed.edu
The main interest of our laboratory has been the biochemical characterization of the
cell-surface receptor on eukaryotic cells for diphtheria toxin, as well as the
characterization of the receptor-binding domain of the toxin.
We have localized the receptor-binding domain of DT to its last 54 amino acids (i.e.,
COOH-end of the B-fragment), and are currently attempting to determine the amino acid
residues in the binding site by employing a combination of synthetic peptides, expression
of this region as a fusion protein expressed in E. coli, and site-directed mutagenesis.
We have recently cloned a diphtheria toxin receptor employing the expression of a
function (i.e., toxin sensitivity) as the screening method; the cloning was accomplished
by transfecting mouse L-cells (which are toxin-resistant) with DNA from monkey kidney
cells (which are highly toxin-sensitive) and by employing a replica plating system for
eukaryotic cells that allowed for the preservation of the toxin-sensitive cells being
sought. We discovered that the transmembrane protein that the toxin employs as a receptor
to gain illicit entry into the cells is a precursor for a growth factor
[called heparin-binding EGF-like growth factor (HB-EGF)]. The precursor for the growth
factor is believed to be synthesized and translocated to the plasma membrane and there it
is processed into the mature (soluble) form of the growth factor, which is the
form found in conditioned media of cells that make this factor. It is during the
cell-surface phase (i.e., in the pro-form) that this protein can be employed by the toxin
as a receptor to enter the cell by receptor-mediated endocytosis. Recently, employing
chimeras and site-directed mutagenesis we have identified the toxin-binding site of the
diphtheria toxin receptor.
Selected Publications:
Cha, J.H., Brooke, J.S., Ivey, K.N., and Eidels, L. (2000) Cell-Surface
Monkey CD9 Antigen is a Coreceptor that Increases Diphtheria Toxin Sensitivity
and Diphtheria Toxin Receptor Affinity. J. Biol. Chem. 275, 6901-6907.
Cha J-H, Brooke JS and Eidels L (1999) Hamster diphtheria toxin receptor: A naturally
occurring chimera of monkey and mouse HB-EGF precursors. Biochem Biophys Res Commun
254, 325-329.
Cha J-H, Brooke JS and Eidels L (1998) Toxin binding site of the diphtheria toxin
receptor: Loss and gain of diphtheria toxin binding of monkey and mouse heparin-binding
epidermal growth factor-like growth factor precursors by reciprocal site-directed
mutagenesis. Molec Microbiol 29, 1275-1284.
Brooke JS, Cha J-H, and Eidels L (1998) Diphtheria toxin: Receptor interaction.
Association, dissociation, and effect of pH. Biochem Biophys Res Commun 248,
297-302.
Hooper KP and Eidels L (1996) Glutamic acid 141 of the diphtheria toxin receptor
(HB-EGF) is critical for toxin binding and toxin sensitivity. Biochem Biophys Res
Commun 220:675-680
Almond BD and Eidels L (1995) The effect of receptor rapid-internalization signals on
diphtheria toxin endocytosis and cell sensitivity. Molec Microbiol 18:623-630
Hooper KP and Eidels L (1995) Localization of a critical diphtheria toxin-binding
domain to the C-terminus of the mature heparin-binding EGF-like growth factor region of
the diphtheria toxin receptor. Biochem Biophys Res Commun 206:710-717
Almond BD and Eidels L (1994) The cytoplasmic domain of the diphtheria toxin receptor
(HB-EFG precursor) is not required for receptor-mediated endocytosis. J Biol Chem
269:26635-26641
Brown JG, Almond BD, Naglich JG, and Eidels L (1993) Hypersensitivity to diphtheria
toxin by mouse cells expressing both diphtheria toxin receptor and CD9 antigen. Proc
Natl Acad Sci USA 90:8184-8188
Naglich JG, Metherall JE, Russell DW and Eidels L (1992) Expression cloning of a
diphtheria toxin receptor: Identity with a heparin-binding EGF-like growth factor
precursor. Cell 69:1051-1061
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Last updated: 16 Aug 2001
Extraction Method: Expand using Medical Synonyms-
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Database: Medline abstracts (1967 - Present)
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