Using our quant approach, we discovered that many sites have similar glycosylation patterns across tissues 🐭We identified sites driving tissue-specificity, enriched in domains involved in cell adhesion, signaling & immunity. E.g., only N445 exhibits tissue specificity on INSR.

It is essential to differentiate surface-exposed glycoforms from intermediate species. To address this, we treated intact living human cells with two enzymes, enabling proteome-wide characterization of mature glycoforms 🧫

To understand structural features governing the level of site microheterogeneity, we leveraged our comprehensive dataset in combination with AlphaFold DB 🖥️

Very little is known about glycoform functionality. We developed a functional glycoproteomics approach enabling the proteome-wide characterization of the solubility of different glycosylated proteoforms in the mouse brain 🐭

We next used our quantitative approach to measure the dynamics of glycosylation changes in human cells treated with a fucosylation inhibitor 🧫 We discovered pervasive site-specific modulation of glycosylation upon perturbation.

We showed remodeling of the mouse brain glycoproteome upon gut microbiome colonization 🐭 The link b/w gut microbiome & brain physiology is long known, but molecular mechanisms remain elusive. We showed that proteins involved in neurotransmission & axon guidance were affected.

Finally, we once again uncovered site-specific modulation of glycosylation upon perturbation, meaning that only some glycoforms on some glycosites are modulated, even within the same protein, suggesting complex regulatory mechanisms.

All data can be interactively explored 🖥️ https://t.co/HEeQVq4UIh. This work was led by Clement Potel, @ https://t.co/wy2qddu82V and @ https://t.co/FcbzPZ1k7o . We thank our great collaborators @ https://t.co/qqrvYwuC0h and @ https://t.co/tzWGTkQKQE.