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

Nat Struct Mol Biol. 2014 May;21(5):489-96. doi: 10.1038/nsmb.2803. Epub 2014 Apr 6.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Cellulose / biosynthesis*
  • Crystallography, X-Ray
  • Cyclic GMP / chemistry*
  • Cyclic GMP / physiology
  • Glucosyltransferases / chemistry*
  • Glucosyltransferases / metabolism
  • Models, Molecular
  • Protein Structure, Tertiary
  • Rhodobacter sphaeroides / enzymology

Substances

  • Bacterial Proteins
  • Cellulose
  • Glucosyltransferases
  • cellulose synthase
  • Cyclic GMP