A molecular description of cellulose biosynthesis

School of Physics Soft Condensed Matter & Physics of Living Systems Seminar: Prof. Jochen Zimmer, University of Virginia

Under certain conditions, essentially all biopolymers, including nucleic acids, proteins and polysaccharides, must be translocated across at least one membrane to reach their final destinations. Cellulose is a linear glucose polymer synthesized and secreted by a membrane-integrated cellulose synthase. We used in crystallo enzymology with the catalytically active bacterial cellulose synthase BcsA–B complex to obtain structural snapshots of a complete cellulose synthesis cycle, from substrate binding to polymer translocation. Substrate- and product-bound structures of BcsA provide the basis for substrate recognition and demonstrate the stepwise elongation of cellulose. Our structural snapshots reveal that BcsA translocates cellulose via a ratcheting mechanism involving a ‘finger helix’ that contacts the polymer’s terminal glucose. Cooperating with BcsA’s gating loop, the finger helix moves ‘up’ and ‘down’ in response to substrate binding and polymer elongation, respectively, thereby pushing the elongated polymer into BcsA’s transmembrane channel. Taken together, our structural and functional analyses reveal how processive membrane integrated glycosyltransferases couple polymer synthesis with translocation.