Structural plasticity and catalysis regulation of a thermosensor histidine kinase

Abstract

Temperature sensing is essential for the survival of living cells. A major challenge is to understand how a biological thermometer processes thermal information to optimize cellular functions. Using structural and biochemical approaches, we show that the thermosensitive histidine kinase, DesK, from Bacillus subtilis is coldactivated through specific interhelical rearrangements in its central four-helix bundle domain. As revealed by the crystal structures of DesK in different functional states, the plasticity of this helical domain influences the catalytic activities of the protein, either by modifying the mobility of the ATP-binding domains for autokinase activity or by modulating binding of the cognate response regulator to sustain the phosphotransferase and phosphatase activities. The structural and biochemical data suggest a model in which the transmembrane sensor domain of DesK promotes these structural changes through conformational signals transmitted by the membrane-connecting two-helical coiled-coil, ultimately controlling the alternation between output autokinase and phosphatase activities. The structural comparison of the different DesK variants indicates that incoming signals can take the form of helix rotations and asymmetric helical bends similar to those reported for other sensing systems, suggesting that a similar switching mechanism could be operational in a wide range of sensor histidine kinases.coiled-coil ͉ conformational rearrangement ͉ crystallography ͉ signal transduction

Sensor–response regulator interactions in a cross-regulated signal transduction network

“…Intragenic complementation results described above for both NarX and NarQ homodimers are compatible only with the intermolecular autophosphorylation mechanism (Yang & Inouye, 1991), in accordance with the structural and biochemical data for DesK (Albanesi et al, 2009;Trajtenberg et al, 2010). This highlights the substantial differences in detail for reaction mechanisms employed by the two transmitter sequence families (Huynh et al, 2010).…”

“…Structural analysis and cross-linking experiments document intermolecular sensor autophosphorylation (Albanesi et al, 2009;Trajtenberg et al, 2010), even though its DHp domain loop is left-handed (Ashenberg et al, 2013). However, unlike the HisKA (HPK1-4) family DHp domains described above, the DesK DHp domain is in the distinct HisKA_3 (HPK7) family together with NarX and NarQ (Grebe & Stock, 1999).…”

“…The NarX DHp domain model (Fig. 1a) was constructed in SWISS-MODEL (Bordoli et al, 2009), and is based on the X-ray structure of the homologous DesK sensor (Albanesi et al, 2009), PDB accession number 3EHJ.…”

Conserved mechanism for sensor phosphatase control of two-component signaling revealed in the nitrate sensor NarX

“…Most systems consist of a sensor protein that exerts both positive and negative control on a cognate response regulator. Well-studied examples include nitrate regulation by NarXNarL, general nitrogen regulation by NtrB-NtrC (also termed NRII-NRI), osmoregulation by EnvZ-OmpR (1), and membrane fluidity regulation by DesK-DesR (2).…”

“…Wellstudied examples of HisKA_3 members include E. coli NarX; Mycobacterium tuberculosis DosS and DosT, which control dormancy (18); Staphylococcus aureus VraS, which mediates cellenvelope stress response (19); and Bacillus subtilis DesK with available transmitter module X-ray structures (2,16).…”