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12:05
Production of Disulfide-stabilized Transmembrane Peptide Complexes for Structural Studies
Published on: March 6, 2013
Generating an unfoldase from thioredoxin-like domains
Michele L Forster1, James J Mahn, Billy Tsai
1Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
The Journal of Biological Chemistry
|March 18, 2009
Summary
Protein-disulfide isomerase (PDI) unfolds cholera toxin A1 (CTA1) via its bb
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Protein-disulfide isomerase (PDI) is an endoplasmic reticulum (ER) protein.
- PDI catalyzes oxidative protein folding and also exhibits protein unfolding activity.
- PDI unfolds cholera toxin A1 (CTA1) to facilitate its retrotranslocation from the ER to the cytosol.
Purpose of the Study:
- To elucidate the mechanism behind PDI's unfoldase activity on CTA1.
- To identify the specific domains and structural arrangements responsible for PDI's unfolding function.
Main Methods:
- Utilized recombinant PDI fragments to dissect domain functions.
- Investigated the binding of CTA1 to different PDI fragments.
- Assessed the role of specific PDI domains (bb', xa', a, a') in CTA1 unfolding.
Main Results:
- The PDIbb'xa' fragment is necessary and sufficient for CTA1 unfolding.
- The linear arrangement of domains and the type of the C-terminal a domain are critical for activity.
- PDI's bb' domains are essential, while the a' domain can be partially substituted by domains from related proteins.
- The a domain of ERp57 inhibits CTA1 binding, preventing it from becoming an unfoldase.
Conclusions:
- PDI's unfoldase activity involves concurrent binding of its bb'xa' domains to specific regions of CTA1, inducing unfolding.
- A functional PDI unfoldase requires the bb'(x) domains followed by an a' domain, without an inhibitory preceding a domain.
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