6QRL

Crystal structure of ShkA _Rec1 in complex with c-di-GMP

Summary for 6QRL

• Entry DOI: 10.2210/pdb6qrl/pdb
• Descriptor: Hybrid kinase, 9,9'-[(2R,3R,3aS,5S,7aR,9R,10R,10aS,12S,14aR)-3,5,10,12-tetrahydroxy-5,12-dioxidooctahydro-2H,7H-difuro[3,2-d:3',2'-j][1,3,7,9,2,8]tetraoxadiphosphacyclododecine-2,9-diyl]bis(2-amino-1,9-dihydro-6H-purin-6-one), SULFATE ION, ... (4 entities in total)
• Functional Keywords: cyclic di-gmp, pseudo receiver domain, second messenger, hybride histidine kinase, shka, auto-inhibition, signaling protein
• Biological source: Caulobacter vibrioides (strain ATCC 19089 / CB15) (Caulobacter crescentus)
• Total number of polymer chains: 2
• Total formula weight: 29429.89

Authors

Dubey, B.N.,Schirmer, T. (deposition date: 2019-02-19, release date: 2020-01-08, Last modification date: 2024-01-24)

Primary citation

Dubey, B.N.,Agustoni, E.,Bohm, R.,Kaczmarczyk, A.,Mangia, F.,von Arx, C.,Jenal, U.,Hiller, S.,Plaza-Menacho, I.,Schirmer, T.
Hybrid histidine kinase activation by cyclic di-GMP-mediated domain liberation.
Proc.Natl.Acad.Sci.USA, 117:1000-1008, 2020

PubMed Abstract: Cytosolic hybrid histidine kinases (HHKs) constitute major signaling nodes that control various biological processes, but their input signals and how these are processed are largely unknown. In , the HHK ShkA is essential for accurate timing of the G1-S cell cycle transition and is regulated by the corresponding increase in the level of the second messenger c-di-GMP. Here, we use a combination of X-ray crystallography, NMR spectroscopy, functional analyses, and kinetic modeling to reveal the regulatory mechanism of ShkA. In the absence of c-di-GMP, ShkA predominantly adopts a compact domain arrangement that is catalytically inactive. C-di-GMP binds to the dedicated pseudoreceiver domain Rec1, thereby liberating the canonical Rec2 domain from its central position where it obstructs the large-scale motions required for catalysis. Thus, c-di-GMP cannot only stabilize domain interactions, but also engage in domain dissociation to allosterically invoke a downstream effect. Enzyme kinetics data are consistent with conformational selection of the ensemble of active domain constellations by the ligand and show that autophosphorylation is a reversible process.

PubMed: 31882446
DOI: 10.1073/pnas.1911427117

Experimental method

X-RAY DIFFRACTION (1.84 Å)