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Recognizing misfolded proteins in the endoplasmic reticulum

Nature Structural Biology volume 7, pages 265–266 (2000)Cite this article

The mechanism by which cells recognize misfolded proteins in the endoplasmic reticulum has been defined at the cell biological level. The enzyme UDP-glucose:glycoprotein glucosyltransferase identifies and specifically glucosylates misfolded domains within a multi-domain protein.

While everyone makes mistakes, it's okay, as long as you notice and fix it. Of course, the hard part is to recognize the mistake. The paper by Ritter and Helenius1 on page 278 of this issue of Nature Structural Biology describes a mechanism by which cells recognize misfolded protein domains in the endoplasmic reticulum in the key step of the quality control system for glycoproteins. Specifically, the authors show in a set of elegant and clear-cut experiments that in the lumen of the endoplasmic reticulum the enzyme UDP-glucose:glycoprotein glucosyltransferase (GT) identifies and glucosylates only the misfolded domains within a protein. Together with earlier work2 by the laboratories of Helenius and others, the paper defines a cell biological process in such detail that it is becoming accessible to biochemical and structural analysis.

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Figure 1: De- and re-glucosylation cycle of the quality control system in the endoplasmic reticulum (ER).

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  1. the Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston , 60208-3500, Illinois, USA

    Andreas Matouschek

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Matouschek, A. Recognizing misfolded proteins in the endoplasmic reticulum. Nat Struct Mol Biol 7, 265–266 (2000). https://doi.org/10.1038/74012

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