4.D.1.1.10
The hyaluronan (hyaluronate) synthase1/exporter, HAS1 of 578 aas and 6 or 7 TMSs in a 1 or 2 TMS(s) (N-terminal) + 5 TMSs (C-terminal) arrangement. Hyaluronan is an acidic heteropolysaccharide comprising alternating N-acetylglucosamine and glucuronate residues that is ubiquitously expressed in the vertebrate extracellular matrix. The high-molecular-mass polymer modulates essential physiological processes in health and disease, including cell differentiation, tissue homeostasis and angiogenesis (Maloney et al. 2022). Hyaluronan is synthesized by a membrane-embedded processive glycosyltransferase, hyaluronan synthase (HAS), which catalyses the synthesis and membrane translocation of hyaluronan from uridine diphosphate-activated precursors. Maloney et al. 2022 described five cryo-EM structures of a viral HAS homologue in different states during substrate binding and initiation of polymer synthesis. HAS selects its substrates, hydrolyses the first substrate to prime the synthesis reaction, opens a hyaluronan-conducting transmembrane channel, ensures alternating substrate polymerization and coordinates hyaluronan inside its transmembrane pore. A detailed model for the formation of an acidic extracellular heteropolysaccharide is proposed that provides insights into the biosynthesis of one of the most abundant and essential glycosaminoglycans in the human body (Maloney et al. 2022).