9yq4

Chlorella virus hyaluronan synthase bound to a proofreading UDP-GlcA

spinqualitylabelsall models 9yq4, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9yq4 is a 3 chain structure with sequence from Lama glama and Paramecium bursaria Chlorella virus CZ-2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.3Å Ligands: MN, UGA, Y01 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Hyaluronan (HA) is an essential polysaccharide of the vertebrate extracellular matrix. It serves as an adhesive, lubricant, signaling molecule, and spatial filler without which embryogenesis would not complete. HA is synthesized by a membrane-integrated glycosyltransferase (HAS) that polymerizes UDP-activated N-acetylglucosamine and glucuronic acid (GlcA) in an alternating fashion. The nascent HA chain is secreted across the plasma membrane during this process. How HAS couples these tasks remains poorly understood. Here, we employ a combination of structural biology, biochemistry and glycobiology to delineate how HAS recognizes and utilizes UDP-GlcA. Using single-particle cryo-EM, we reveal a two-step process by which HAS binds its substrate UDP-GlcA. Prior to proper insertion into the catalytic pocket, the substrate is bound in a proofreading pose that may increase substrate selectivity. This state is accompanied by conformational changes of active site residues surrounding the UDP-binding pocket and involves a pair of basic residues that sense the substrate's carboxyl group. Further, we establish that HAS is unable to catalyze UDP-GlcA turnover in the absence of an acceptor sugar, emphasizing the role of a priming GlcNAc in glycosyl transfer. Lastly, cryo-EM snapshots of a dodecylmaltoside molecule trapped in the active site provide novel insights into substrate promiscuity. Here, our studies demonstrate that HAS catalyzes semi-selective GlcA-transfer to non-canonical beta-linked acceptors. Insights into substrate binding and utilization by hyaluronan synthase.,Stephens Z, Karasinska J, Zimmer J bioRxiv [Preprint]. 2025 Oct 18:2025.10.17.683186. doi: , 10.1101/2025.10.17.683186. PMID:41280022 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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