Structural basis of glycoprotein recognition by the human folding sensor UDP-glucose:glycoprotein glucosyltransferase.

Cryo-EM structures of human full-length UGGT1 reveal open and closed conformations, with a bridging density in the open state linking TRXL2 to the catalytic domain.

• Why it matters: UGGT1 quality control depends on recognizing misfolded glycoprotein clients, but the molecular basis of how its sensory region engages the catalytic machinery was unclear.
• What they did: The authors determined cryo-EM structures of monomeric and dimeric UGGT1, used 3D variability and molecular dynamics to infer intermediate states, and mapped endogenous client N-glycosylation sites by glycoproteomics.
• The result: The open-state density supports substrate association near the catalytic domain, while dimerization occludes substrate binding sites; glycoproteomics found no consensus flanking modified sites and disease-linked UGGT1 variants are explained by the human structure.

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