Structural basis of glycoprotein quality control system

Abstract

  The sugar chains operate as tags for intracellular quality control of glycoproteins, ensuring their appropriate folding and trafficking in cells. Especially, in the endoplasmic reticulum, the folding states of newly synthesized proteins are recognized through the presence or absence of only a single terminal glucose residue. These key processes involving glucose-trimming and attachment are executed by actions of glucosidase II and UDP-glucose/glycoprotein glucosyltransferase (UGGT), respectively. Recently, the eukaryotic multi-domain, large enzymes that are generally difficult to crystallize, were successfully crystallized by utilizing thermophilic fungi as the source organisms. This review summarizes a recently emerging evidence regarding structural basis of the functional mechanisms of these key enzymes, as provided by X-ray crystallography in conjunction with a series of biophysical techniques, including small-angle X-ray scattering, high-speed atomic force microscopy and electron microscopy, which are capable of providing dynamic views of these enzymes in solution.