Structural basis of KdpD histidine kinase binding to the second messenger c-di-AMP

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved..

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 (USPSa) complexed with c-di-AMP. Binding affinity analyses of USPSa mutants targeting the observed USPSa: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)XSXSX2N(Y/F), which allowed us to predict c-di-AMP binding in other KdpD HKs. Furthermore, we found that the USPSa 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 USPSa-like domains in KdpD HKs represent a novel subfamily of the USPs.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:296

Enthalten in:

The Journal of biological chemistry - 296(2021) vom: 06. Jan., Seite 100771

Sprache:

Englisch

Beteiligte Personen:

Dutta, Anirudha [VerfasserIn]
Batish, Mona [VerfasserIn]
Parashar, Vijay [VerfasserIn]

Links:

Volltext

Themen:

Bacterial Proteins
Bacterial signal transduction
C-di-AMP
Crystal structure
Cyclic AMP
E0399OZS9N
EC 2.7.-
EC 2.7.13.1
Histidine Kinase
Histidine kinase
Journal Article
KdpD protein, Bacteria
Methicillin-resistant Staphylococcus aureus
Osmoregulation
Protein Kinases
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Second messenger

Anmerkungen:

Date Completed 31.08.2021

Date Revised 07.11.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.jbc.2021.100771

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM325409927