Biochemical evidence for an alternate pathway in N-linked glycoprotein biosynthesis
Name
Imperiali_Biochemical evidence.pdf
Size
575.64 KB
Format
Adobe PDF
Checksum (MD5)
4e38e932afcba55804879a328f4d5a67
Author(s)
Larkin, Angelyn
Imperiali, Barbara
Chang, Michelle
Whitworth, Garrett
Date Issued
April 2013
Journal
Nature Chemical Biology
Publisher
Nature Publishing Group
Citation
Larkin, Angelyn, Michelle M Chang, Garrett E Whitworth, and Barbara Imperiali. “Biochemical Evidence for an Alternate Pathway in N-Linked Glycoprotein Biosynthesis.” Nat Chem Biol 9, no. 6 (April 28, 2013): 367–373.
Version
Author's final manuscript
Abstract
Asparagine-linked glycosylation is a complex protein modification conserved among all three domains of life. Herein we report the in vitro analysis of N-linked glycosylation from the methanogenic archaeon Methanococcus voltae. Using a suite of synthetic and semisynthetic substrates, we show that AglK initiates N-linked glycosylation in M. voltae through the formation of α-linked dolichyl monophosphate N-acetylglucosamine, which contrasts with the polyprenyl diphosphate intermediates that feature in both eukaryotes and bacteria. Notably, AglK has high sequence homology to dolichyl phosphate β-glucosyltransferases, including Alg5 in eukaryotes, suggesting a common evolutionary origin. The combined action of the first two enzymes, AglK and AglC, afforded an α-linked dolichyl monophosphate glycan that serves as a competent substrate for the archaeal oligosaccharyl transferase AglB. These studies provide what is to our knowledge the first biochemical evidence revealing that, despite the apparent similarity of the overall pathways, there are actually two general strategies to achieve N-linked glycoproteins across the domains of life.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/nchembio.1249
