7JI4

Universal stress protein (USP) domain of KdpD histidine kinase in complex with second messenger c-di-AMP

Summary for 7JI4

• Entry DOI: 10.2210/pdb7ji4/pdb
• Descriptor: KdpD, (2R,3R,3aS,5R,7aR,9R,10R,10aS,12R,14aR)-2,9-bis(6-amino-9H-purin-9-yl)octahydro-2H,7H-difuro[3,2-d:3',2'-j][1,3,7,9,2,8 ]tetraoxadiphosphacyclododecine-3,5,10,12-tetrol 5,12-dioxide (3 entities in total)
• Functional Keywords: universal stress protein, histidine kinase, second messenger, two component system, signaling protein
• Biological source: Staphylococcus aureus subsp. aureus MRSA252
• Total number of polymer chains: 1
• Total formula weight: 18311.95

Authors

Dutta, A.,Parashar, V. (deposition date: 2020-07-22, release date: 2021-05-26, Last modification date: 2024-03-06)

Primary citation

Dutta, A.,Batish, M.,Parashar, V.
Structural basis of KdpD histidine kinase binding to the second messenger c-di-AMP.
J.Biol.Chem., 296:100771-100771, 2021

PubMed Abstract: The KdpDE two-component system regulates potassium homeostasis and virulence in various bacterial species. The KdpD histidine kinases (HK) of this system contain a universal stress protein (USP) domain which binds to the second messenger cyclic-di-adenosine monophosphate (c-di-AMP) for regulating transcriptional output from this two-component system in Firmicutes such as Staphylococcus aureus. However, the structural basis of c-di-AMP specificity within the KdpD-USP domain is not well understood. Here, we resolved a 2.3 Å crystal structure of the S. aureus KdpD-USP domain (USP) complexed with c-di-AMP. Binding affinity analyses of USP mutants targeting the observed USP:c-di-AMP structural interface enabled the identification of the sequence residues that are required for c-di-AMP specificity. Based on the conservation of these residues in other Firmicutes, we identified the binding motif, (A/G/C)XSXSXN(Y/F), which allowed us to predict c-di-AMP binding in other KdpD HKs. Furthermore, we found that the USP domain contains structural features distinct from the canonical standalone USPs that bind ATP as a preferred ligand. These features include inward-facing conformations of its β1-α1 and β4-α4 loops, a short α2 helix, the absence of a triphosphate-binding Walker A motif, and a unique dual phospho-ligand binding mode. It is therefore likely that USP-like domains in KdpD HKs represent a novel subfamily of the USPs.

PubMed: 33989637
DOI: 10.1016/j.jbc.2021.100771

Experimental method

X-RAY DIFFRACTION (2.3 Å)