Source 1primary paper2014Proceedings of the National Academy of Sciences
Toolkit/dimerization/histidine phosphotransfer-like (DHpL) domain
dimerization/histidine phosphotransfer-like (DHpL) domain
Also known as: DHpL domain
Taxonomy: Mechanism Branch / Component. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
The dimerization/histidine phosphotransfer-like (DHpL) domain is a regulatory domain element within the blue-light-responsive histidine kinase EL346. Structural evidence indicates that, in the dark, interactions involving the LOV sensor domain and the DHpL domain stabilize an inhibited kinase conformation and suppress dimerization, while photoactivation weakens these contacts to promote activation.
Usefulness & Problems
Why this is useful
This domain is useful as a mechanistic handle for understanding how light input is coupled to histidine kinase regulation in EL346. The available evidence supports its role as a central interface through which the LOV sensor modulates kinase activity and oligomeric state.
Problem solved
The DHpL domain helps explain how a monomeric blue-light-responsive histidine kinase can be held inactive in the dark and activated upon illumination. Specifically, it addresses the structural basis by which sensory-domain binding inhibits kinase output and prevents dimerization.
Problem links
Need conditional control of signaling activity
DerivedThe dimerization/histidine phosphotransfer-like (DHpL) domain is a regulatory domain element within the blue-light-responsive histidine kinase EL346. In the reported structural model, one side of the DHpL domain is bound by the LOV sensor domain in the dark, contributing to inhibition of kinase activity and suppression of dimerization, with light weakening these interdomain contacts to promote activation.
Need precise spatiotemporal control with light input
DerivedThe dimerization/histidine phosphotransfer-like (DHpL) domain is a regulatory domain element within the blue-light-responsive histidine kinase EL346. In the reported structural model, one side of the DHpL domain is bound by the LOV sensor domain in the dark, contributing to inhibition of kinase activity and suppression of dimerization, with light weakening these interdomain contacts to promote activation.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Component: A low-level protein part used inside a larger architecture that realizes a mechanism.
Mechanisms
allosteric switchingallosteric switchingdimerization suppressionHeterodimerizationHeterodimerizationlight-weakened interdomain interactionlight-weakened interdomain interactionTechniques
No technique tags yet.
Target processes
signalingInput: Light
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: multi component delivery burdenimplementation constraint: spectral hardware requirementoperating role: sensorswitch architecture: multi componentswitch architecture: recruitmentswitch architecture: uncaging
The supplied evidence places the DHpL domain in the context of full-length EL346, where it functions through contacts with both the LOV sensor domain and the catalytic ATP-binding (CA) domain. The input modality is blue light, but the evidence does not provide construct design rules, expression conditions, or standalone deployment guidance for the DHpL domain.
The evidence is limited to a single reported structural and mechanistic study in EL346, so generality beyond this protein is not established. No independent replication, engineering optimization, or broad functional benchmarking of the isolated DHpL domain is provided in the supplied evidence.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
The DHpL domain contacts the CA domain and keeps EL346 in an inhibited conformation in the dark.
The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark.
The DHpL domain contacts the CA domain and keeps EL346 in an inhibited conformation in the dark.
The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark.
The DHpL domain contacts the CA domain and keeps EL346 in an inhibited conformation in the dark.
The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark.
The DHpL domain contacts the CA domain and keeps EL346 in an inhibited conformation in the dark.
The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark.
The DHpL domain contacts the CA domain and keeps EL346 in an inhibited conformation in the dark.
The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark.
The DHpL domain contacts the CA domain and keeps EL346 in an inhibited conformation in the dark.
The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark.
The DHpL domain contacts the CA domain and keeps EL346 in an inhibited conformation in the dark.
The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark.
The DHpL domain contacts the CA domain and keeps EL346 in an inhibited conformation in the dark.
The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark.
The DHpL domain contacts the CA domain and keeps EL346 in an inhibited conformation in the dark.
The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark.
The DHpL domain contacts the CA domain and keeps EL346 in an inhibited conformation in the dark.
The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark.
The DHpL domain contacts the CA domain and keeps EL346 in an inhibited conformation in the dark.
The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark.
The DHpL domain contacts the CA domain and keeps EL346 in an inhibited conformation in the dark.
The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark.
The DHpL domain contacts the CA domain and keeps EL346 in an inhibited conformation in the dark.
The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark.
The DHpL domain contacts the CA domain and keeps EL346 in an inhibited conformation in the dark.
The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark.
The DHpL domain contacts the CA domain and keeps EL346 in an inhibited conformation in the dark.
The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark.
The DHpL domain contacts the CA domain and keeps EL346 in an inhibited conformation in the dark.
The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark.
The DHpL domain contacts the CA domain and keeps EL346 in an inhibited conformation in the dark.
The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark.
The LOV sensor domain controls kinase activity and prevents dimerization by binding one side of the DHpL domain.
Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain.
The LOV sensor domain controls kinase activity and prevents dimerization by binding one side of the DHpL domain.
Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain.
The LOV sensor domain controls kinase activity and prevents dimerization by binding one side of the DHpL domain.
Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain.
The LOV sensor domain controls kinase activity and prevents dimerization by binding one side of the DHpL domain.
Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain.
The LOV sensor domain controls kinase activity and prevents dimerization by binding one side of the DHpL domain.
Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain.
The LOV sensor domain controls kinase activity and prevents dimerization by binding one side of the DHpL domain.
Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain.
The LOV sensor domain controls kinase activity and prevents dimerization by binding one side of the DHpL domain.
Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain.
The LOV sensor domain controls kinase activity and prevents dimerization by binding one side of the DHpL domain.
Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain.
The LOV sensor domain controls kinase activity and prevents dimerization by binding one side of the DHpL domain.
Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain.
The LOV sensor domain controls kinase activity and prevents dimerization by binding one side of the DHpL domain.
Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain.
The LOV sensor domain controls kinase activity and prevents dimerization by binding one side of the DHpL domain.
Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain.
The LOV sensor domain controls kinase activity and prevents dimerization by binding one side of the DHpL domain.
Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain.
The LOV sensor domain controls kinase activity and prevents dimerization by binding one side of the DHpL domain.
Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain.
The LOV sensor domain controls kinase activity and prevents dimerization by binding one side of the DHpL domain.
Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain.
The LOV sensor domain controls kinase activity and prevents dimerization by binding one side of the DHpL domain.
Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain.
The LOV sensor domain controls kinase activity and prevents dimerization by binding one side of the DHpL domain.
Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain.
The LOV sensor domain controls kinase activity and prevents dimerization by binding one side of the DHpL domain.
Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain.
The LOV domain controls kinase activity by affecting stability of the DHpL/CA interface and releasing the CA domain from an inhibited conformation upon photoactivation.
Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation.
The LOV domain controls kinase activity by affecting stability of the DHpL/CA interface and releasing the CA domain from an inhibited conformation upon photoactivation.
Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation.
The LOV domain controls kinase activity by affecting stability of the DHpL/CA interface and releasing the CA domain from an inhibited conformation upon photoactivation.
Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation.
The LOV domain controls kinase activity by affecting stability of the DHpL/CA interface and releasing the CA domain from an inhibited conformation upon photoactivation.
Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation.
The LOV domain controls kinase activity by affecting stability of the DHpL/CA interface and releasing the CA domain from an inhibited conformation upon photoactivation.
Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation.
The LOV domain controls kinase activity by affecting stability of the DHpL/CA interface and releasing the CA domain from an inhibited conformation upon photoactivation.
Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation.
The LOV domain controls kinase activity by affecting stability of the DHpL/CA interface and releasing the CA domain from an inhibited conformation upon photoactivation.
Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation.
The LOV domain controls kinase activity by affecting stability of the DHpL/CA interface and releasing the CA domain from an inhibited conformation upon photoactivation.
Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation.
The LOV domain controls kinase activity by affecting stability of the DHpL/CA interface and releasing the CA domain from an inhibited conformation upon photoactivation.
Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation.
The LOV domain controls kinase activity by affecting stability of the DHpL/CA interface and releasing the CA domain from an inhibited conformation upon photoactivation.
Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation.
The LOV domain controls kinase activity by affecting stability of the DHpL/CA interface and releasing the CA domain from an inhibited conformation upon photoactivation.
Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation.
The LOV domain controls kinase activity by affecting stability of the DHpL/CA interface and releasing the CA domain from an inhibited conformation upon photoactivation.
Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation.
The LOV domain controls kinase activity by affecting stability of the DHpL/CA interface and releasing the CA domain from an inhibited conformation upon photoactivation.
Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation.
The LOV domain controls kinase activity by affecting stability of the DHpL/CA interface and releasing the CA domain from an inhibited conformation upon photoactivation.
Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation.
The LOV domain controls kinase activity by affecting stability of the DHpL/CA interface and releasing the CA domain from an inhibited conformation upon photoactivation.
Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation.
The LOV domain controls kinase activity by affecting stability of the DHpL/CA interface and releasing the CA domain from an inhibited conformation upon photoactivation.
Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation.
The LOV domain controls kinase activity by affecting stability of the DHpL/CA interface and releasing the CA domain from an inhibited conformation upon photoactivation.
Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation.
Light stimulation weakens interdomain interactions to facilitate EL346 activation.
Upon light stimulation, interdomain interactions weaken to facilitate activation.
Light stimulation weakens interdomain interactions to facilitate EL346 activation.
Upon light stimulation, interdomain interactions weaken to facilitate activation.
Light stimulation weakens interdomain interactions to facilitate EL346 activation.
Upon light stimulation, interdomain interactions weaken to facilitate activation.
Light stimulation weakens interdomain interactions to facilitate EL346 activation.
Upon light stimulation, interdomain interactions weaken to facilitate activation.
Light stimulation weakens interdomain interactions to facilitate EL346 activation.
Upon light stimulation, interdomain interactions weaken to facilitate activation.
Light stimulation weakens interdomain interactions to facilitate EL346 activation.
Upon light stimulation, interdomain interactions weaken to facilitate activation.
Light stimulation weakens interdomain interactions to facilitate EL346 activation.
Upon light stimulation, interdomain interactions weaken to facilitate activation.
Light stimulation weakens interdomain interactions to facilitate EL346 activation.
Upon light stimulation, interdomain interactions weaken to facilitate activation.
Light stimulation weakens interdomain interactions to facilitate EL346 activation.
Upon light stimulation, interdomain interactions weaken to facilitate activation.
Light stimulation weakens interdomain interactions to facilitate EL346 activation.
Upon light stimulation, interdomain interactions weaken to facilitate activation.
EL346 functions as a monomer rather than as a dimeric histidine kinase.
Contrary to the standard view that signaling occurs within HK dimers, EL346 functions as a monomer.
EL346 functions as a monomer rather than as a dimeric histidine kinase.
Contrary to the standard view that signaling occurs within HK dimers, EL346 functions as a monomer.
EL346 functions as a monomer rather than as a dimeric histidine kinase.
Contrary to the standard view that signaling occurs within HK dimers, EL346 functions as a monomer.
EL346 functions as a monomer rather than as a dimeric histidine kinase.
Contrary to the standard view that signaling occurs within HK dimers, EL346 functions as a monomer.
EL346 functions as a monomer rather than as a dimeric histidine kinase.
Contrary to the standard view that signaling occurs within HK dimers, EL346 functions as a monomer.
EL346 functions as a monomer rather than as a dimeric histidine kinase.
Contrary to the standard view that signaling occurs within HK dimers, EL346 functions as a monomer.
EL346 functions as a monomer rather than as a dimeric histidine kinase.
Contrary to the standard view that signaling occurs within HK dimers, EL346 functions as a monomer.
EL346 functions as a monomer rather than as a dimeric histidine kinase.
Contrary to the standard view that signaling occurs within HK dimers, EL346 functions as a monomer.
EL346 functions as a monomer rather than as a dimeric histidine kinase.
Contrary to the standard view that signaling occurs within HK dimers, EL346 functions as a monomer.
EL346 functions as a monomer rather than as a dimeric histidine kinase.
Contrary to the standard view that signaling occurs within HK dimers, EL346 functions as a monomer.
Approval Evidence
1 source3 linked approval claimsfirst-pass slug dimerization-histidine-phosphotransfer-like-dhpl-domain
by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain
Source:
dark state inhibitionsupports
The DHpL domain contacts the CA domain and keeps EL346 in an inhibited conformation in the dark.
The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark.
Source:
mechanism of regulationsupports
The LOV sensor domain controls kinase activity and prevents dimerization by binding one side of the DHpL domain.
Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain.
Source:
mechanistic modelsupports
The LOV domain controls kinase activity by affecting stability of the DHpL/CA interface and releasing the CA domain from an inhibited conformation upon photoactivation.
Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation.
Source:
Comparisons
Source-backed strengths
A full-length structural study provides direct evidence that one side of the DHpL domain is bound by the LOV sensor domain and that the DHpL domain contacts the CA domain in the inhibited dark state. The mechanistic model further links photoactivation to destabilization of the DHpL/CA interface and release of the CA domain from inhibition.
Compared with light-oxygen-voltage sensing (LOV) domain
dimerization/histidine phosphotransfer-like (DHpL) domain and light-oxygen-voltage sensing (LOV) domain address a similar problem space because they share signaling.
Shared frame: same top-level item type; shared target processes: signaling; shared mechanisms: heterodimerization; same primary input modality: light
Relative tradeoffs: looks easier to implement in practice.
Compared with optogenetic RGS2
dimerization/histidine phosphotransfer-like (DHpL) domain and optogenetic RGS2 address a similar problem space because they share signaling.
Shared frame: same top-level item type; shared target processes: signaling; shared mechanisms: heterodimerization; same primary input modality: light
Relative tradeoffs: looks easier to implement in practice.
dimerization/histidine phosphotransfer-like (DHpL) domain and photoactivatable inhibitor for cyclic-AMP dependent kinase (PKA) address a similar problem space because they share signaling.
Shared frame: same top-level item type; shared target processes: signaling; shared mechanisms: allosteric switching; same primary input modality: light
Relative tradeoffs: looks easier to implement in practice.
Ranked Citations
- 1.