6D9M

T4-Lysozyme fusion to Geobacter GGDEF

Summary for 6D9M

• Entry DOI: 10.2210/pdb6d9m/pdb
• Descriptor: Fusion protein of Endolysin,Response receiver sensor diguanylate cyclase, GAF domain-containing, GUANOSINE-5'-TRIPHOSPHATE, GUANOSINE, ... (8 entities in total)
• Functional Keywords: cyclic dinucleotide, ggdef, hydrolase
• Biological source: Enterobacteria phage T4 (Bacteriophage T4); More
• Total number of polymer chains: 1
• Total formula weight: 39830.53

Authors

Hallberg, Z.,Doxzen, K.,Kranzusch, P.J.,Hammond, M. (deposition date: 2018-04-30, release date: 2019-04-10, Last modification date: 2024-03-13)

Primary citation

Hallberg, Z.F.,Chan, C.H.,Wright, T.A.,Kranzusch, P.J.,Doxzen, K.W.,Park, J.J.,Bond, D.R.,Hammond, M.C.
Structure and mechanism of a Hypr GGDEF enzyme that activates cGAMP signaling to control extracellular metal respiration.
Elife, 8:-, 2019

PubMed Abstract: A newfound signaling pathway employs a GGDEF enzyme with unique activity compared to the majority of homologs associated with bacterial cyclic di-GMP signaling. This system provides a rare opportunity to study how signaling proteins natively gain distinct function. Using genetic knockouts, riboswitch reporters, and RNA-Seq, we show that GacA, the Hypr GGDEF in , specifically regulates cyclic GMP-AMP (3',3'-cGAMP) levels in vivo to stimulate gene expression associated with metal reduction separate from electricity production. To reconcile these in vivo findings with prior in vitro results that showed GacA was promiscuous, we developed a full kinetic model combining experimental data and mathematical modeling to reveal mechanisms that contribute to in vivo specificity. A 1.4 Å-resolution crystal structure of the Hypr GGDEF domain was determined to understand the molecular basis for those mechanisms, including key cross-dimer interactions. Together these results demonstrate that specific signaling can result from a promiscuous enzyme.

PubMed: 30964001
DOI: 10.7554/eLife.43959

Experimental method

X-RAY DIFFRACTION (1.35 Å)