Dolichyl-phosphate beta-glucosyltransferase

Dolichyl-phosphate beta-glucosyltransferase (DPGT) is an essential enzyme involved in the biosynthesis of N-linked glycoproteins. It plays a crucial role in the transfer of glucose residues to dolichyl phosphate, a lipid carrier molecule, during the early stages of protein glycosylation in the endoplasmic reticulum (ER) of eukaryotic cells.

Function

DPGT catalyzes the transfer of glucose from UDP-glucose to dolichyl phosphate, resulting in the formation of dolichyl phosphate glucose (Dol-P-Glc). This reaction is a key step in the assembly of the lipid-linked oligosaccharide (LLO) precursor, which serves as a donor for N-linked glycosylation. The LLO precursor is subsequently transferred to nascent polypeptides in the ER lumen, where further glycosylation modifications occur.

Structure

DPGT is a transmembrane protein located in the ER membrane. It consists of multiple transmembrane domains that anchor the enzyme in the lipid bilayer, with the active site facing the ER lumen. The enzyme contains a conserved catalytic domain, which is responsible for the transfer of glucose residues to dolichyl phosphate.

Role in N-linked glycosylation

N-linked glycosylation is a post-translational modification process that involves the attachment of oligosaccharide chains to specific asparagine residues in target proteins. This modification is crucial for protein folding, stability, and function. DPGT plays a vital role in the early steps of N-linked glycosylation by providing the glucose moiety for the LLO precursor.

Clinical significance

Mutations in the DPGT gene have been associated with a rare genetic disorder known as congenital disorder of glycosylation type Ie (CDG-Ie). CDG-Ie is characterized by a deficiency in DPGT activity, leading to impaired protein glycosylation. This can result in a wide range of symptoms, including developmental delays, intellectual disability, and various organ dysfunctions.