Structural diversity in a conserved cholera toxin epitope involved in ganglioside binding

Protein Science : a Publication of the Protein Society
M ShohamW G Hol

Abstract

Cholera is a widespread disease for which there is no efficient vaccine. A better understanding of the conformational rearrangements at the epitope might be very helpful for the development of a good vaccine. Cholera toxin (CT) as well as the closely related heat-labile toxin from Escherichia coli (LT) are composed of two subunits, A and B, which form an oligomeric assembly AB5. Residues 50-64 on the surface of the B subunits comprise a conserved loop (CTP3), which is involved in saccharide binding to the receptor on epithelial cells. This loop exhibits remarkable conformational plasticity induced by environmental constraints. The crystal structure of this loop is compared in the free and receptor-bound toxins as well as in the crystal and solution structures of a complex with TE33, a monoclonal antibody elicited against CTP3. In the toxins this loop forms an irregular structure connecting a beta-strand to the central alpha-helix. Ser 55 and Gln 56 exhibit considerable conformational variability in the five subunits of the unliganded toxins. Saccharide binding induces a change primarily in Ser 55 and Gln 56 to a conformation identical in all five copies. Thus, saccharide binding confers rigidity upon the loop. The conformation ...Continue Reading

References

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Feb 1, 1994·Protein Science : a Publication of the Protein Society·E A MerrittW G Hol
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Citations

Nov 28, 2001·Applied and Environmental Microbiology·K KjaergaardP Klemm
Apr 23, 2008·Journal of Chemical Information and Modeling·Hiroaki FukunishiJiro Shimada
Nov 28, 2016·Progress in Nuclear Magnetic Resonance Spectroscopy·Jacob AnglisterFred Naider

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