Northampton Electronic Collection of Theses and Research

Folding-competent and folding-defective forms of Ricin A Chain have different fates after retrotranslocation from the Endoplasmic Reticulum

Li, S., Spooner, R. A., Allen, S. C. H., Guise, C. P., Ladds, G., Schnoder, T., Schmitt, M. J., Lord, J. M. and Roberts, R. M. (2010) Folding-competent and folding-defective forms of Ricin A Chain have different fates after retrotranslocation from the Endoplasmic Reticulum. Molecular Biology of the Cell. 21(15), pp. 2543-2554. 1059-1524.

Item Type: Article
Abstract: We report that a toxic polypeptide retaining the potential to refold upon dislocation from the endoplasmic reticulum (ER) to the cytosol (ricin A chain; RTA) and a misfolded version that cannot (termed RTA), follow ER-associated degradation (ERAD) pathways in Saccharomyces cerevisiae that substantially diverge in the cytosol. Both polypeptides are dislocated in a step mediated by the transmembrane Hrd1p ubiquitin ligase complex and subsequently degraded. Canonical polyubiquitylation is not a prerequisite for this interaction because a catalytically inactive Hrd1p E3 ubiquitin ligase retains the ability to retrotranslocate RTA, and variants lacking one or both endogenous lysyl residues also require the Hrd1p complex. In the case of native RTA, we established that dislocation also depends on other components of the classical ERAD-L pathway as well as an ongoing ER–Golgi transport. However, the dislocation pathways deviate strikingly upon entry into the cytosol. Here, the CDC48 complex is required only for RTA, although the involvement of individual ATPases (Rpt proteins) in the 19S regulatory particle (RP) of the proteasome, and the 20S catalytic chamber itself, is very different for the two RTA variants. We conclude that cytosolic ERAD components, particularly the proteasome RP, can discriminate between structural features of the same substrate.
Subjects: Q Science > QH Natural history > QH573 Cytology
Q Science > QR Microbiology
Creators: Li, S, Spooner, R A, Allen, Stuart C H, Guise, C P, Ladds, G, Schnoder, T, Schmitt, M J, Lord, J M and Roberts, R M
Publisher: American Society for Cell Biology
Faculties, Divisions and Institutes: University Faculties, Divisions and Research Centres - OLD > Faculty of Health & Society > Sports, Exercise & Life Sciences
Faculties > Faculty of Health & Society > Sports, Exercise & Life Sciences
Date: 2 June 2010
Date Type: Publication
Page Range: pp. 2543-2554
Journal or Publication Title: Molecular Biology of the Cell
Volume: 21
Number: 15
Language: English
DOI: https://doi.org/10.1091/mbc.E09-08-0743
ISSN: 1059-1524
Status: Published / Disseminated
Refereed: Yes
URI: http://nectar.northampton.ac.uk/id/eprint/3302

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