(9) Deep gratitude to everyone who made this possible —my postdoc mentor @carolynbertozzi.bskyverified.social, brilliant friends & collaborators @miratsojitra.bsky.social, @tomislavcaval.bsky.social, @andrenmateus.bsky.social and my (former) mentors @hecklab.bsky.social & @savitski-lab.bsky.social.

(9) Deep gratitude to everyone who made this possible —my postdoc mentor @carolynbertozzi.bskyverified.social, brilliant friends & collaborators @miratsojitra.bsky.social, @tomislavcaval.bsky.social, @andrenmateus.bsky.social, and my (former) mentors @hecklab.bsky.social & @savitski-lab.bsky.social.

(8) Bottom line: Understanding glycosylation's functional impact requires more than cataloging which glycans are attached. We hope this resource helps the community dissect glycan-protein relationships at scale!

(7) How does fucose loss impair binding? MD simulations reveal that core fucose normally restricts glycan dynamics, preserving protein flexibility. Without it, the glycan samples a larger conformational space—shielding the Ca²⁺ site and forming new contacts that constrain integrin dynamics.

(6) Can our systems-level data also yield single-protein insights? YES! We focused on integrin α4—fucose loss reduced thermal stability and impaired VCAM-1 binding. Notably, this is the interaction targeted by natalizumab in multiple sclerosis.

(5) To dig deeper, we applied TPCA (thermal proximity co-aggregation) analysis. This revealed that altered glycosylation triggers widespread protein complex remodeling—shifting interaction dynamics in ways consistent with the cellular pivot from secretion to degradation.

(4) What happens when glycosylation goes wrong? Perhaps unsurprisingly, cells mount convergent stress responses across diverse perturbations. The common denominator: coordinated trafficking reorganization that redirects protein flux from secretion → degradation.

(3) Our approach: Perturb the secretory pathway to generate distinct glycan structures, then use thermal proteome profiling (TPP) as a discovery tool. Glycoproteomics, chemical glycobiology & MD simulations then reveal how altered glycosylation drives these changes mechanistically.

(2) Glycosylation shapes protein folding, stability & interactions. Aberrant glycosylation marks many diseases, including cancer—but how does it actually impact protein function? We can catalog glycoforms well, yet we felt that a workflow to connect them to protein function at scale were missing.

Congrats Tereza and team - very cool paper!