Structural highlights
Publication Abstract from PubMed
In the endoplasmic reticulum (ER), a protein quality control system facilitates the efficient folding of newly synthesised proteins. In this system, a series of N-linked glycan intermediates displayed on the protein surface serve as quality tags. The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes. Here we characterise the dynamic structure of this enzyme. Our crystallographic data demonstrate that the sensor region is composed of four thioredoxin-like domains followed by a beta-rich domain, which are arranged into a C-shaped structure with a large central cavity, while the C-terminal catalytic domain undergoes a ligand-dependent conformational alteration. Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements. These findings provide structural insights into the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates.
Visualisation of a flexible modular structure of the ER folding-sensor enzyme UGGT.,Satoh T, Song C, Zhu T, Toshimori T, Murata K, Hayashi Y, Kamikubo H, Uchihashi T, Kato K Sci Rep. 2017 Sep 22;7(1):12142. doi: 10.1038/s41598-017-12283-w. PMID:28939828[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Satoh T, Song C, Zhu T, Toshimori T, Murata K, Hayashi Y, Kamikubo H, Uchihashi T, Kato K. Visualisation of a flexible modular structure of the ER folding-sensor enzyme UGGT. Sci Rep. 2017 Sep 22;7(1):12142. doi: 10.1038/s41598-017-12283-w. PMID:28939828 doi:https://dx.doi.org/10.1038/s41598-017-12283-w
