9Q8Z

Human chondroitin sulfate polymerase complex CHSY3-CHPF

Summary for 9Q8Z

• Entry DOI: 10.2210/pdb9q8z/pdb
• EMDB information: 52913
• Descriptor: Chondroitin sulfate synthase 2, Chondroitin sulfate synthase 3, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: glycosyltransferase, chondroitin sulfate, polymerization, heterodimeric complex, transferase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 166481.66

Authors

Dutta, P.,Cordeiro, R.L.,Wild, R. (deposition date: 2025-02-25, release date: 2025-12-03, Last modification date: 2026-01-07)

Primary citation

Dutta, P.,Cordeiro, R.L.,Friedel-Arboleas, M.,Bourgeais, M.,Vallet, S.D.,Weber, M.,Molinas, M.,Shu, H.,Gronset, M.N.N.,Miller, R.L.,Boeri Erba, E.,Wild, R.
Structural basis for human chondroitin sulfate chain polymerization.
Nat Commun, 16:11663-11663, 2025

PubMed Abstract: Chondroitin sulfates are complex polysaccharide chains that regulate various biological processes at the cell surface and within the extracellular matrix. Here, we identify four heterodimeric complexes responsible for chondroitin sulfate chain polymerization in humans: CHSY1-CHPF, CHSY1-CHPF2, CHSY3-CHPF, and CHSY3-CHPF2. Using a custom-tailored in vitro glycosylation assay based on chemo-enzymatically synthesized fluorescent substrates, we demonstrate that all four complexes exhibit chain polymerization activity. The cryo-EM structure of the CHSY3-CHPF complex provides molecular insights into the chondroitin sulfate chain polymerization reaction. The architecture of the catalytic sites suggests that CHSY1 and CHSY3 are enzymatically active, while CHPF and CHPF2 primarily play a stabilizing role. Mutational analysis of purified enzyme complexes, combined with an in cellulo complementation assay, confirms that only CHSY1 and CHSY3 have bifunctional glycosyltransferase activities. Based on the spatial arrangement of the catalytic sites, we propose that chondroitin sulfate chain polymerization follows a non-processive, distributive mechanism.

PubMed: 41298522
DOI: 10.1038/s41467-025-66787-5

Experimental method

ELECTRON MICROSCOPY (3 Å)