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Science 7 May 1999:
Vol. 284. no. 5416, pp. 955 - 957
DOI: 10.1126/science.284.5416.955
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Reports

Interaction of Diphtheria Toxin T Domain with Molten Globule-Like Proteins and Its Implications for Translocation

Jianhua Ren, 1* Kelli Kachel, 1* Hyun Kim, 1 Susan E. Malenbaum, 1 R. John Collier, Erwin London 1ddagger

The transmembrane (T) domain of diphtheria toxin has a critical role in the low pH-induced translocation of the catalytic domain (A chain) of the toxin across membranes. Here it is shown that at low pH, addition of proteins in a partly unfolded, molten globule-like conformation converted the T domain from a shallow membrane-inserted form to its transmembrane form. Fluorescence energy transfer demonstrated that molten globule-like proteins bound to the T domain. Thus, the T domain recognizes proteins that are partly unfolded and may function in translocation of the A chain as a transmembrane chaperone.

1 Department of Biochemistry and Cell Biology and Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
2 Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
*   These authors contributed equally to this work.

ddagger    To whom correspondence should be addressed. E-mail: elondon{at}ccmail.sunysb.edu

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