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.
