PLOD3

Procollagen-lysine,2-oxoglutarate 5-dioxygenase 3 is an enzyme that in humans is encoded by the PLOD3 gene.
The protein encoded by this gene is a membrane-bound homodimeric enzyme that is localized to the cisternae of the rough endoplasmic reticulum. The enzyme catalyzes the hydroxylation of lysyl residues in collagen-like peptides. The resultant hydroxylysyl groups are attachment sites for carbohydrates in collagen and thus are critical for the stability of intermolecular crosslinks. Some patients with Ehlers-Danlos syndrome type VIB have deficiencies in lysyl hydroxylase activity.

Structure and functions

Cryo-electron microscopy study has revealed the structural architecture of PLOD3 within the lysyl O-linked glycosylation complex, which plays a crucial role in procollagen maturation.
The KOGG complex consists of a PLOD3 dimer, a Procollagen galactosyltransferase 1 dimer, and UDP-bound cofactors, orchestrating the hydroxylation and dual glycosylation of lysine residues in the endoplasmic reticulum lumen. These modifications are essential for collagen cross-linking, fibrillogenesis, and overall structural integrity.
Additionally, the structural study suggests that the KOGG complex can polymerize into a larger, fiber-like enzyme supercomplex, which may further regulate collagen modification and assembly. Defects in PLOD3 function or glycosylation efficiency have been implicated in connective tissue disorders, including osteogenesis imperfecta and fibrosis-related diseases.