8ZGC

Human lysine O-link glycosylation complex, LH3/ColGalT1 with bound UDP-galactose

Summary for 8ZGC

• Entry DOI: 10.2210/pdb8zgc/pdb
• EMDB information: 60075
• Descriptor: Multifunctional procollagen lysine hydroxylase and glycosyltransferase LH3, Procollagen galactosyltransferase 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: complex, hydroxylase, glycosyltransferase, er protein, cytosolic protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 664226.27

Authors

Peng, J.,Li, W.,Yao, D.,Xia, Y.,Wang, Q.,Cai, Y.,Li, S.,Cao, M.,Shen, Y.,Ma, P.,Liao, R.,Qin, A.,Cao, Y. (deposition date: 2024-05-09, release date: 2025-03-19, Last modification date: 2025-03-26)

Primary citation

Peng, J.,Li, W.,Yao, D.,Xia, Y.,Wang, Q.,Cai, Y.,Li, S.,Cao, M.,Shen, Y.,Ma, P.,Liao, R.,Zhao, J.,Qin, A.,Cao, Y.
The structural basis for the human procollagen lysine hydroxylation and dual-glycosylation.
Nat Commun, 16:2436-2436, 2025

PubMed Abstract: The proper assembly and maturation of collagens necessitate the orchestrated hydroxylation and glycosylation of multiple lysyl residues in procollagen chains. Dysfunctions in this multistep modification process can lead to severe collagen-associated diseases. To elucidate the coordination of lysyl processing activities, we determine the cryo-EM structures of the enzyme complex formed by LH3/PLOD3 and GLT25D1/ColGalT1, designated as the KOGG complex. Our structural analysis reveals a tetrameric complex comprising dimeric LH3/PLOD3s and GLT25D1/ColGalT1s, assembled with interactions involving the N-terminal loop of GLT25D1/ColGalT1 bridging another GLT25D1/ColGalT1 and LH3/PLOD3. We further elucidate the spatial configuration of the hydroxylase, galactosyltransferase, and glucosyltransferase sites within the KOGG complex, along with the key residues involved in substrate binding at these enzymatic sites. Intriguingly, we identify a high-order oligomeric pattern characterized by the formation of a fiber-like KOGG polymer assembled through the repetitive incorporation of KOGG tetramers as the biological unit.

PubMed: 40069201
DOI: 10.1038/s41467-025-57768-9

Experimental method

ELECTRON MICROSCOPY (3.58 Å)