Mechanism of activation of bacterial cellulose synthase by cyclic di-GMP

• DOI: 10.1038/nsmb.2803
• Publication Date: 2014-04-06T23:00:00Z
• Authors: Jacob L W Morgan; Joshua T McNamara; Jochen Zimmer
• Keywords: Models, Molecular; 0301 basic medicine; Binding Sites; Rhodobacter sphaeroides; Crystallography, X-Ray; Article; Protein Structure, Tertiary; 03 medical and health sciences; Bacterial Proteins; Glucosyltransferases; Cellulose; Cyclic GMP

The bacterial signaling molecule cyclic di-GMP (c-di-GMP) stimulates the synthesis of bacterial cellulose, which is frequently found in biofilms. Bacterial cellulose is synthesized and translocated across the inner membrane by a complex of cellulose synthase BcsA and BcsB subunits. Here we present crystal structures of the c-di-GMP-activated BcsA-BcsB complex. The structures reveal that c-di-GMP releases an autoinhibited state of the enzyme by breaking a salt bridge that otherwise tethers a conserved gating loop that controls access to and substrate coordination at the active site. Disrupting the salt bridge by mutagenesis generates a constitutively active cellulose synthase. Additionally, the c-di-GMP-activated BcsA-BcsB complex contains a nascent cellulose polymer whose terminal glucose unit rests at a new location above BcsA's active site and is positioned for catalysis. Our mechanistic insights indicate how c-di-GMP allosterically modulates enzymatic functions.