6QRJ

Crystal structure of ShkA full-length in complex with AMPPNP

Summary for 6QRJ

• Entry DOI: 10.2210/pdb6qrj/pdb
• Descriptor: Hybrid kinase, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: cyclic di-gmp, second messenger, hybride histidine kinase, shka, auto-inhibitio, signaling protein
• Biological source: Caulobacter vibrioides CB15
• Total number of polymer chains: 1
• Total formula weight: 50830.86

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 (2.65 Å)