Structural basis of the molecular ruler mechanism of a bacterial glycosyltransferase

Ramírez, Ana S.; Boilevin, Jérémy; Mehdipour, Ahmad Reza; Hummer, Gerhard; Darbre, Tamis; Reymond, Jean-Louis; Locher, Kaspar P. (2018). Structural basis of the molecular ruler mechanism of a bacterial glycosyltransferase. Nature communications, 9(1) Nature Publishing Group 10.1038/s41467-018-02880-2

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The membrane-associated, processive and retaining glycosyltransferase PglH from Campylobacter jejuni is part of the biosynthetic pathway of the lipid-linked oligosaccharide (LLO) that serves as the glycan donor in bacterial protein N-glycosylation. Using an unknown counting mechanism, PglH catalyzes the transfer of exactly three α1,4 N-acetylgalactosamine (GalNAc) units to the growing LLO precursor, GalNAc-α1,4-GalNAc-α1,3-Bac-α1-PP-undecaprenyl. Here, we present crystal structures of PglH in three distinct states, including a binary complex with UDP-GalNAc and two ternary complexes containing a chemo-enzymatically generated LLO analog and either UDP or synthetic, nonhydrolyzable UDP-CH2-GalNAc. PglH contains an amphipathic helix (“ruler helix”) that has a dual role of facilitating membrane attachment and glycan counting. The ruler helix contains three positively charged side chains that can bind the pyrophosphate group of the LLO substrate and thus limit the addition of GalNAc units to three. These results, combined with molecular dynamics simulations, provide the mechanism of glycan counting by PglH.

Item Type:

Journal Article (Original Article)


08 Faculty of Science > Departement of Chemistry and Biochemistry

UniBE Contributor:

Boilevin, Jérémy Mathias; Darbre, Tamis and Reymond, Jean-Louis


500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry




Nature Publishing Group




Sandra Tanja Zbinden Di Biase

Date Deposited:

19 Dec 2018 14:14

Last Modified:

23 Dec 2018 02:33

Publisher DOI:





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