Rapid simulation of glycoprotein structures by grafting and steric exclusion of glycan conformer libraries

Archaea produce various protein filaments with specialised functions. While some archaea produce only one type of filament, the archaeal model species Sulfolobus acidocaldarius generates four. These include rotary swimming propellers analogous to bacterial flagella (archaella), pili for twitching motility (Aap), adhesive fibres (threads), and filaments facilitating homologous recombination upon UV stress (UV pili). Here, we use cryo-electron microscopy to describe the structure of the S. acidocaldarius archaellum at 2.0 Å resolution, and update the structures of the thread and the Aap pilus at 2.7 Å and 2.6 Å resolution, respectively. We define features unique to archaella of the order Sulfolobales and compare their structure to those of Aap and threads in the context of the S-layer. We define distinct N-glycan patterns in the three filaments and identify a putative O-glycosylation site in the thread. Finally, we ascertain whether N-glycan truncation leads to structural changes in archaella and Aap.

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Restoring protein glycosylation with GlycoShape

Ives,

Singh,

D’Andrea

et al. 2024

Nat Methods

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Despite ground-breaking innovations in experimental structural biology and protein structure prediction techniques, capturing the structure of the glycans that functionalize proteins remains a challenge. Here we introduce GlycoShape (https://glycoshape.org), an open-access glycan structure database and toolbox designed to restore glycoproteins to their native and functional form in seconds. The GlycoShape database counts over 500 unique glycans so far, covering the human glycome and augmented by elements from a wide range of organisms, obtained from 1 ms of cumulative sampling from molecular dynamics simulations. These structures can be linked to proteins with a robust algorithm named Re-Glyco, directly compatible with structural data in open-access repositories, such as the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) and AlphaFold Protein Structure Database, or own. The quality, performance and broad applicability of GlycoShape is demonstrated by its ability to predict N-glycosylation occupancy, scoring a 93% agreement with experiment, based on screening all proteins in the PDB with a corresponding glycoproteomics profile, for a total of 4,259 N-glycosylation sequons.

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Rapid simulation of glycoprotein structures by grafting and steric exclusion of glycan conformer libraries

Cited by 10 publications

References 122 publications

Constructing a highly sensitive duplex immunoassay using AuNPs and AgNPs as nanolabels for investigating the epithelial-mesenchymal transition occurring on circulating tumor cells with lung cancer patients

Constructing a highly sensitive duplex immunoassay using AuNPs and AgNPs as nanolabels for investigating the epithelial-mesenchymal transition occurring on circulating tumor cells with lung cancer patients

Towards a molecular picture of the archaeal cell surface

Restoring protein glycosylation with GlycoShape

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