PXD072144 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Functional assays of human ALG9 |
| Description | Asparagine-linked glycans are essential for the maturation and function of most eukaryotic secretory proteins. Biosynthesis and transfer of the GlcNAc2Man9Glc3 glycan occurs on the endoplasmic reticulum (ER) membrane, in a highly conserved process involving more than a dozen membrane proteins whose dysfunction is linked to severe congenital disorders of glycosylation (CDGs). Three membrane-integral mannosyltransferases ALG3, ALG9 and ALG12 mediate four consecutive mannosylation reactions that convert GlcNAc2Man5 to GlcNAc2Man9. Using chemo-enzymatically synthesised lipid-linked glycan donor and acceptor analogues, we recapitulated this biosynthetic pathway in vitro. High-resolution cryo-EM structures of pseudo-Michaelis complexes of each step revealed the molecular basis of how the branched glycan is accurately synthesised in sequential reactions. Molecular dynamics simulations, mutagenesis, and functional assays uncovered a subtle but high precision mechanisms selecting the dolichylphosphomannose donor substrate over the also present epimer, dolichylphosphoglucose. Together, our results provide mechanistic explanations for enzyme disfunction in CDG and offer opportunities for N-glycan engineering. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-05-30 |
| AnnouncementXML | Submission_2026-05-30_05:57:40.094.xml |
| DigitalObjectIdentifier | https://doi.org/10.6019/PXD072144 |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | J. Andrew Alexander |
| SpeciesList | scientific name: synthetic construct; NCBI TaxID: NEWT:32630; |
| ModificationList | amidated residue |
| Instrument | Orbitrap Fusion Lumos |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-12-18 06:56:13 | ID requested | |
| ⏵ 1 | 2026-05-30 05:57:40 | announced | |
Publication List
Keyword List
| submitter keyword: ALG9, oligomannose, N-glycans |
Contact List
| Kaspar P. Locher |
|---|
| contact affiliation | Institute of Molecular Biology and Biophysics, Eidgenössische Technische Hochschule (ETH) Zürich, Zürich, Switzerland |
| contact email | locher@mol.biol.ethz.ch |
| lab head | |
| J. Andrew Alexander |
|---|
| contact affiliation | ETH Zürich |
| contact email | andrew.alexander@mol.biol.ethz.ch |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/05/PXD072144 |
| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD072144
- Label: PRIDE project
- Name: Functional assays of human ALG9
