Recognition and ER Quality Control of Misfolded Formylglycine-Generating Enzyme by Protein Disulfide Isomerase

Schlotawa L, Wachs M, Bernhard O, Mayer FJ, Dierks T, Schmidt B, Radhakrishnan K (2018)
Cell Reports 24(1): 27-37.e4.

Zeitschriftenaufsatz | Veröffentlicht| Englisch
 
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Schlotawa, Lars; Wachs, MichaelaUniBi; Bernhard, Olaf; Mayer, Franz J.; Dierks, ThomasUniBi; Schmidt, Bernhard; Radhakrishnan, KarthikeyanUniBi
Abstract / Bemerkung
Multiple sulfatase deficiency (MSD) is a fatal, inherited lysosomal storage disorder characterized by reduced activities of all sulfatases in patients. Sulfatases require a unique post-translational modification of an active-site cysteine to formylglycine that is catalyzed by the formylglycine-generating enzyme (FGE). FGE mutations that affect intracellular protein stability determine residual enzyme activity and disease severity in MSD patients. Here, we show that protein disulfide isomerase (PDI) plays a pivotal role in the recognition and quality control of MSD-causing FGE variants. Overexpression of PDI reduces the residual activity of unstable FGE variants, whereas inhibition of PDI function rescues the residual activity of sulfatases in MSD fibroblasts. Mass spectrometric analysis of a PDI+FGE variant covalent complex allowed determination of the molecular signature for FGE recognition by PDI. Our findings highlight the role of PDI as a disease modifier in MSD, which may also be relevant for other ER-associated protein folding pathologies.
Erscheinungsjahr
2018
Zeitschriftentitel
Cell Reports
Band
24
Ausgabe
1
Seite(n)
27-37.e4
eISSN
2211-1247
Finanzierungs-Informationen
Article Processing Charge funded by the Deutsche Forschungsgemeinschaft and the Open Access Publication Fund of Bielefeld University.
Page URI
https://pub.uni-bielefeld.de/record/2921018

Zitieren

Schlotawa L, Wachs M, Bernhard O, et al. Recognition and ER Quality Control of Misfolded Formylglycine-Generating Enzyme by Protein Disulfide Isomerase. Cell Reports. 2018;24(1):27-37.e4.
Schlotawa, L., Wachs, M., Bernhard, O., Mayer, F. J., Dierks, T., Schmidt, B., & Radhakrishnan, K. (2018). Recognition and ER Quality Control of Misfolded Formylglycine-Generating Enzyme by Protein Disulfide Isomerase. Cell Reports, 24(1), 27-37.e4. doi:10.1016/j.celrep.2018.06.016
Schlotawa, L., Wachs, M., Bernhard, O., Mayer, F. J., Dierks, T., Schmidt, B., and Radhakrishnan, K. (2018). Recognition and ER Quality Control of Misfolded Formylglycine-Generating Enzyme by Protein Disulfide Isomerase. Cell Reports 24, 27-37.e4.
Schlotawa, L., et al., 2018. Recognition and ER Quality Control of Misfolded Formylglycine-Generating Enzyme by Protein Disulfide Isomerase. Cell Reports, 24(1), p 27-37.e4.
L. Schlotawa, et al., “Recognition and ER Quality Control of Misfolded Formylglycine-Generating Enzyme by Protein Disulfide Isomerase”, Cell Reports, vol. 24, 2018, pp. 27-37.e4.
Schlotawa, L., Wachs, M., Bernhard, O., Mayer, F.J., Dierks, T., Schmidt, B., Radhakrishnan, K.: Recognition and ER Quality Control of Misfolded Formylglycine-Generating Enzyme by Protein Disulfide Isomerase. Cell Reports. 24, 27-37.e4 (2018).
Schlotawa, Lars, Wachs, Michaela, Bernhard, Olaf, Mayer, Franz J., Dierks, Thomas, Schmidt, Bernhard, and Radhakrishnan, Karthikeyan. “Recognition and ER Quality Control of Misfolded Formylglycine-Generating Enzyme by Protein Disulfide Isomerase”. Cell Reports 24.1 (2018): 27-37.e4.
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2019-09-06T09:19:00Z
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