5Y7F

Crystal structure of catalytic domain of UGGT (UDP-bound form) from Thermomyces dupontii

Summary for 5Y7F

• Entry DOI: 10.2210/pdb5y7f/pdb
• Related: 5H18
• Descriptor: UGGT, URIDINE-5'-DIPHOSPHATE, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (5 entities in total)
• Functional Keywords: endoplasmic reticulum, quality control, glucosyltransferase, folding sensor, transferase
• Biological source: Thermomyces dupontii
• Total number of polymer chains: 1
• Total formula weight: 35664.00

Authors

Satoh, T.,Song, C.,Zhu, T.,Toshimori, T.,Murata, K.,Hayashi, Y.,Kamikubo, H.,Uchihashi, T.,Kato, K. (deposition date: 2017-08-17, release date: 2017-09-27, Last modification date: 2024-10-23)

Primary citation

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, 7:12142-12142, 2017

PubMed Abstract: 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 β-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.

PubMed: 28939828
DOI: 10.1038/s41598-017-12283-w

Experimental method

X-RAY DIFFRACTION (1.35 Å)