Insights into the Molecular Basis of Biofilm Dispersal from Crystal Structures of Didomain Containing Proteins

  • Julien LescarEmail author


Biofilm formation by bacterial pathogens is a serious public health issue because it increases resistance to antibiotics and significant efforts have been spent to understand its molecular basis. Bis-(3′5′)-cyclic dimeric guanosine monophosphate (cyclic di-GMP) is a second messenger involved in the regulation of bacterial motility, virulence, and biofilm formation. The amount of cyclic di-GMP results from the balance between its synthesis from GTP by diguanylate cyclases (GGDEF domains) and hydrolysis by enzymes bearing the EAL or HD-GYP motif. In bacterial genomes, GGDEF and EAL domains are frequently linked. This family of proteins comprises N-terminal sensor domain(s) followed by a GGDEF and an EAL domain. We call these proteins “didomain-containing proteins.” Here we briefly review recent structural data on didomain-containing proteins that originated from various investigators. Taken together, these structures suggest how the level of cyclic di-GMP is allosterically regulated in response to the environment. Didomain-containing proteins appear as key components in a network of molecular devices that have evolved to detect and integrate various environmental signals. Upon signal detection, evolutionary conserved helices adjust the quaternary structure of the individual domains, leading to an adequate enzymatic activity and a contextually optimal level of cyclic di-GMP.


Cyclic di-GMP Sensor domain GGDEF-EAL domain Pseudomonas aeruginosa Biofilm Crystal structure Allosteric control 



We thank scientists and staff on the MXI, MXII (Australian Synchrotron, Clayton, Victoria) and PXIII (Paul Scherrer Institut, Switzerland) beamlines, for their expert assistance. This work was supported by an AcRF Tier 1 grant RG154/14 to the J.L. and Scott A. Rice laboratories.


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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.School of Biological Sciences, Nanyang Technological UniversitySingaporeSingapore
  2. 2.NTU Institute of Structural Biology, Nanyang Technological University, Experimental Medicine BuildingSingaporeSingapore

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