Hyaluronan (HA) is a linear polysaccharide of alternating N-acetyl-glucosamine and glucuronic acid residues and constitutes a major component of the extracellular matrix in vertebrates. HA is synthesized on the cytosolic side of the cell membrane by the membrane-embedded hyaluronan synthase (HAS). However, the process by which the highly charged HA polymer is translocated across the membrane is unknown to date. We demonstrate that the purified and reconstituted HAS from Streptococcus equisimilis translocates HA across the vesicle membrane during its synthesis. The newly formed polysaccharide remains tightly associated with the lipid vesicles and is protected from enzymatic degradation by hyaluronidase, unless the proteoliposomes are solubilized. The HAS therefore couples HA elongation with translocation, a reaction mechanism that is likely applicable to the synthesis of some of the most abundant biopolymers, including chitin and cellulose.

Hyaluronan synthases catalyze the synthesis and membrane translocation of hyaluronan

243rd National Meeting (2012)

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