Interdomain conformational flexibility underpins the activity of UGGT, the eukaryotic glycoprotein secretion checkpoint
Abstract
A dedicated endoplasmic reticulum quality control (ERQC) machinery ensures the correct fold of secreted proteins bearing N-linked glycans, which constitute around a fifth of the whole proteome and are essential for many important cellular processes such as signaling, immunity, adhesion, transport, and metabolism. UDP-glucose:glycoprotein glucosyltransferase (UGGT) is the sole checkpoint enzyme of ERQC, flagging incorrectly folded glycoproteins for ER retention. Here, we describe crystal structures of full-length UGGT. We show that enzymatic activity depends on interdomain conformational mobility, indicating that the intrinsic flexibility of UGGT may endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- August 2017
- DOI:
- 10.1073/pnas.1703682114
- Bibcode:
- 2017PNAS..114.8544R