Hyaluronan Synthase: The Mechanism of Initiation at the Reducing End and a Pendulum Model for Polysaccharide Translocation to the Cell Exterior

Figure 7

The Pendulum Model: Arm movement and HA transfer between arms drives HA chain translocation through the HAS⋅lipid complex to the cell exterior. The changing alignment of the HA-binding regions on the two arms in the two extreme positions (left and right) creates the ability of the enzyme to move the HA chain from one arm to the other (shown in each row). When the arms swing from one extreme position to the other, the HA chain is transferred from the first arm to the other arm as the HA-binding site alignments move out of (neutral position) and then back into register. A “time-lapse” of HAS action is illustrated in the nine panels as the enzyme adds three new sugars to an HA-UDP chain of seven sugars. The enzyme goes through three stages of arm movement (in each row) to add each new sugar. After assembly of each disaccharide, the enzyme arms are in the same starting position (e.g., the left panels in top and bottom rows). The sugars “crossing” the membrane are shown outside of the enzyme in the top row to help orient the reader, and then within the intraprotein pore in the middle and bottom rows. An animation of this process showing chain translocation through assembly of an HA 10-mer is at http://www.glycoforum.gr.jp/science/hyaluronan/HA06a/Pendulum_Hypothesis_Anima.files/slide0001.htm.