Mechanism of activation of bacterial cellulose synthase by cyclic di-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.
Center for Membrane Biology, Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA.
Jacob L W
JL
Morgan
Center for Membrane Biology, Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA.
Joshua T
JT
McNamara
Center for Membrane Biology, Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA.
Jochen
J
Zimmer
D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002482:Cellulose / Q000096:biosynthesis*; D018360:Crystallography, X-Ray; D006152:Cyclic GMP / Q000737:chemistry* / Q000502:physiology; D005964:Glucosyltransferases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D012242:Rhodobacter sphaeroides / Q000201:enzymology
D001426:Bacterial Proteins; D002482:Cellulose; D005964:Glucosyltransferases; C478648:cellulose synthase; D006152:Cyclic GMP