The pertussis toxin S1 subunit is a thermally unstable protein susceptible to degradation by the 20S proteasome

    Authors

    A. H. Pande; D. Moe; M. Jamnadas; S. A. Tatulian;K. Teter

    Comments

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    Abbreviated Journal Title

    Biochemistry

    Keywords

    RICIN-A-CHAIN; ENDOPLASMIC-RETICULUM; CHOLERA-TOXIN; ADP-RIBOSYLATION; EUKARYOTIC CELLS; INTRACELLULAR TRAFFICKING; SELECTIVE DEGRADATION; RETROGRADE TRANSPORT; ADENINE-NUCLEOTIDES; OXIDIZED CALMODULIN; Biochemistry & Molecular Biology

    Abstract

    Pertussis toxin ( PT) is an AB-type protein toxin that consists of a catalytic A subunit ( PT S1) and an oligomeric, cell-binding B subunit. It belongs to a subset of AB toxins that move from the cell surface to the endoplasmic reticulum ( ER) before the A chain passes into the cytosol. Toxin translocation is thought to involve A chain unfolding in the ER and the quality control mechanism of ER-associated degradation ( ERAD). The absence of lysine residues in PT S1 may allow the translocated toxin to avoid ubiquitin-dependent degradation by the 26S proteasome, which is the usual fate of exported ERAD substrates. As the conformation of PT S1 appears to play an important role in toxin translocation, we used biophysical and biochemical methods to examine the structural properties of PT S1. Our in vitro studies found that the isolated PT S1 subunit is a thermally unstable protein that can be degraded in a ubiquitin-independent fashion by the core 20S proteasome. The thermal denaturation of PT S1 was inhibited by its interaction with NAD, a donor molecule used by PT S1 for the ADP ribosylation of target G proteins. These observations support a model of intoxication in which toxin translocation, degradation, and activity are all influenced by the heat-labile nature of the isolated toxin A chain.

    Journal Title

    Biochemistry

    Volume

    45

    Issue/Number

    46

    Publication Date

    1-1-2006

    Document Type

    Article

    Language

    English

    First Page

    13734

    Last Page

    13740

    WOS Identifier

    WOS:000242021100006

    ISSN

    0006-2960

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