RT Journal Article
SR Electronic
T1 Activation mechanism of a small prototypic Rec-GGDEF diguanylate cyclase
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.28.271692
DO 10.1101/2020.08.28.271692
A1 Raphael D. Teixeira
A1 Fabian Holzschuh
A1 Tilman Schirmer
YR 2020
UL http://biorxiv.org/content/early/2020/08/28/2020.08.28.271692.abstract
AB Diguanylate cyclases (DGCs) synthesising the bacterial second messenger c-di-GMP are found to be regulated by a variety of sensory input domains that control the activity of their catalytical GGDEF domain. As part of two-component systems, they are activated by cognate histidine kinases that phosphorylate their Rec input domains. DgcR from Leptospira biflexa is a constitutively dimeric prototype of this class of DGCs. Full-length crystal structures revealed that BeF3- pseudo-phosphorylation induces a relative rotation of two rigid halves in the Rec domain. This is coupled to a reorganisation of the dimeric structure with concomitant switching of the coiled-coil linker to an alternative heptad register. Finally, the activated register allows the two substrate-loaded GGDEF domains, which are linked to the end of the coiled-coil via a localised hinge, to move into a catalytically competent dimeric arrangement. Bioinformatic analyses suggest that the binary register switch mechanism is utilised by many DGCs with N-terminal coiled-coil linkers.Competing Interest StatementThe authors have declared no competing interest.