Glycoprotein folding, quality control and ER-associated degradation

Gerardo Z. Lederkremer*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

194 Scopus citations

Abstract

Nascent N-linked glycoproteins possess a large oligosaccharide precursor, Glc3Man9GlcNAc2, which is later sequentially trimmed. Recent studies help understand the code displayed by each structure produced by this trimming and its decoding by lectins. The calnexin folding cycle targets only monoglucosylated oligosaccharides. N-glycans of misfolded glycoproteins are then more extensively trimmed than once thought, being targeted for degradation by removal of three or four mannose residues. A high local concentration of endoplasmic reticulum (ER) mannosidase I in an ER-derived quality control compartment is mainly responsible for this trimming, with the possible participation of other mannosidases. The shortened chains, Man5-6GlcNAc2, are recognized by the ubiquitination machinery-associated lectin OS9 but not by lectins that associate with properly folded glycoproteins en route to the Golgi that bind best to Man8-9GlcNAc2.

Original languageEnglish
Pages (from-to)515-523
Number of pages9
JournalCurrent Opinion in Structural Biology
Volume19
Issue number5
DOIs
StatePublished - Oct 2009

Funding

FundersFunder number
DIP
German-Israeli Project Cooperation
Kodesz Institute
Israel Cancer Association
Israel Science Foundation1229/07

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