8SND

Chlorella virus Hyaluronan Synthase bound to GlcNAc primer and UDP-GlcA

Summary for 8SND

• Entry DOI: 10.2210/pdb8snd/pdb
• EMDB information: 40623
• Descriptor: Hyaluronan synthase, Nanobody 872, Nanobody 881, ... (9 entities in total)
• Functional Keywords: hyaluronic acid, hyaluronan, ha, has, glycosyltransferase, gt, membrane protein, nanobody, n-acetylglucosamine, glucuronic acid, transferase
• Biological source: Paramecium bursaria Chlorella virus CZ-2; More
• Total number of polymer chains: 3
• Total formula weight: 98074.22

Authors

Stephens, Z.,Zimmer, J. (deposition date: 2023-04-27, release date: 2024-05-01, Last modification date: 2025-02-05)

Primary citation

Gorniak, I.,Stephens, Z.,Erramilli, S.K.,Gawda, T.,Kossiakoff, A.A.,Zimmer, J.
Structural insights into translocation and tailored synthesis of hyaluronan.
Nat.Struct.Mol.Biol., 32:161-171, 2025

PubMed Abstract: Hyaluronan (HA) is an essential component of the vertebrate extracellular matrix. It is a heteropolysaccharide of N-acetylglucosamine (GlcNAc) and glucuronic acid (GlcA) reaching several megadaltons in healthy tissues. HA is synthesized and translocated in a coupled reaction by HA synthase (HAS). Here, structural snapshots of HAS provide insights into HA biosynthesis, from substrate recognition to HA elongation and translocation. We monitor the extension of a GlcNAc primer with GlcA, reveal the coordination of the uridine diphosphate product by a conserved gating loop and capture the opening of a translocation channel to coordinate a translocating HA polymer. Furthermore, we identify channel-lining residues that modulate HA product lengths. Integrating structural and biochemical analyses suggests an avenue for polysaccharide engineering based on finely tuned enzymatic activity and HA coordination.

PubMed: 39322765
DOI: 10.1038/s41594-024-01389-1

Experimental method

ELECTRON MICROSCOPY (3.1 Å)