Bacterial DnaK/DnaJ/GrpE protein refolding cycle

A bacterial cytosolic Hsp70 refolding module in which the Hsp40 co-chaperone DnaJ captures unfolded or misfolded clients, stimulates DnaK ATP hydrolysis through its J domain, and promotes substrate locking onto DnaK; GrpE then drives nucleotide exchange to reset the DnaK cycle and release clients for folding. The sigma32/RpoH feedback branch, ClpB-dependent disaggregation, and DnaK's ATP-independent holdase side activity are outside this focused DnaK/DnaJ/GrpE folding cycle.

MODULE:bacterial_dnak_dnaj_refolding_cycleDRAFTCONCRETEBiological Processmodules/bacterial_dnak_dnaj_refolding_cycle.yaml

protein refoldingGO:0042026 ATP-dependent protein folding chaperoneGO:0140662 ATPase activator activityGO:0001671 adenyl-nucleotide exchange factor activityGO:0000774

GO:0140662

ATP-dependent protein folding chaperone

Defines DnaK's ATP-dependent client-remodeling activity.

GO:0001671

ATPase activator activity

Defines DnaJ stimulation of the DnaK ATPase cycle.

file:genes/ECOLI/DnaK/DnaK-ai-review.yaml

ECOLI DnaK gene review

The completed E. coli DnaK review grounds DnaK as the Hsp70 ATP-dependent protein folding chaperone of the DnaK/DnaJ/GrpE cycle.

file:genes/ECOLI/DnaJ/DnaJ-ai-review.yaml

ECOLI DnaJ gene review

The completed E. coli DnaJ review grounds DnaJ as the Hsp40 client targeting and DnaK ATPase-activating co-chaperone.

file:genes/ECOLI/grpE/grpE-ai-review.yaml

ECOLI grpE gene review

The completed E. coli grpE review grounds GrpE as the DnaK adenyl-nucleotide exchange factor.

PMID:1826368

Escherichia coli DnaJ and GrpE heat shock proteins jointly stimulate ATPase activity of DnaK.

Establishes the stimulation of DnaK ATPase activity by DnaJ and GrpE.

PMID:7937953

The ATP hydrolysis-dependent reaction cycle of the Escherichia coli Hsp70 system DnaK, DnaJ, and GrpE.

Supports ATP-dependent DnaK/DnaJ cycles as a core route for efficient client folding.

PMID:20953191

The kinetic parameters and energy cost of the Hsp70 chaperone as a polypeptide unfoldase.

Quantifies the DnaK/DnaJ/GrpE machine as a polypeptide unfoldase that uses ATP to remodel stable misfolded clients.

The completed DnaK, DnaJ, and GrpE ECOLI reviews cover the canonical Hsp70 refolding machine. The module leaves out DnaJ-independent DnaK functions, GrpE's temperature-tuned heat-shock feedback role, and other J-domain paralogs.

4Nodes

3Parts

0Variant Sets

0Variants

3Annotons

3Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:bacterial_dnak_dnaj_refolding_cycle deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

3 gene-function check(s) reflected in core functions · 0 conflict(s) · 0 evidence or coverage gap(s) (3 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

Annoton	Participant	Function	Assessment
dnaj_atpase_activation	E. coli DnaJ UniProtKB:P08622 Gene	DnaK ATPase activator activity GO:0001671	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnak_atp_dependent_chaperone	E. coli DnaK UniProtKB:P0A6Y8 Gene	ATP-dependent protein folding chaperone GO:0140662	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
grpe_nucleotide_exchange_factor	E. coli GrpE UniProtKB:P09372 Gene	adenyl-nucleotide exchange factor activity GO:0000774	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).

Gene-review completeness (3/3 grounded genes reviewed)

3 complete review(s) · 2 with deep research · 0 missing review · 1 reviewed but lacking deep research

Gene	Review	Complete	Deep research
DnaJ P08622	✓	✓	✓
DnaK P0A6Y8	✓	✓	✓
grpE P09372	✓	✓	✗

Tree

Bacterial DnaK/DnaJ/GrpE protein refolding cycleBiological Processbacterial_dnak_dnaj_refolding_cycle

Parts
1. 1. DnaJ client capture and DnaK ATPase stimulation
2. DnaJ-stimulated client loading onto DnaKReactiondnaj_client_delivery
  
  Annotons
  - DnaJ ATPase-activating co-chaperone Gene Product: E. coli DnaJ
3. 2. DnaK ATP-coupled client remodeling
4. DnaK ATP-dependent client remodelingReactiondnak_client_remodeling
  
  Annotons
  - DnaK ATP-dependent folding chaperone Gene Product: E. coli DnaK
5. 3. GrpE nucleotide exchange and DnaK reset
6. GrpE-catalyzed DnaK nucleotide exchangeReactiongrpe_nucleotide_exchange
  
  Annotons
  - GrpE DnaK nucleotide-exchange factor Gene Product: E. coli GrpE

Details

Context

bacteriaNCBITaxon:2

Bacterial DnaK/DnaJ/GrpE protein refolding cycleBiological Processbacterial_dnak_dnaj_refolding_cycle

protein refoldingGO:0042026 ATP-dependent protein folding chaperoneGO:0140662 ATPase activator activityGO:0001671 adenyl-nucleotide exchange factor activityGO:0000774

Context

bacteriaNCBITaxon:2

Connections

dnaj_client_delivery -> dnak_client_remodeling Provides Input For

dnak_client_remodeling -> grpe_nucleotide_exchange Provides Input For

grpe_nucleotide_exchange -> dnaj_client_delivery Provides Input For

Part 1: DnaJ client capture and DnaK ATPase stimulation

DnaJ-stimulated client loading onto DnaKReactiondnaj_client_delivery

DnaJ binds non-native client proteins and uses its J domain to stimulate ATP hydrolysis by DnaK, stabilizing the client-loaded DnaK-ADP state.

Annotons

DnaJ ATPase-activating co-chaperone

dnaj_atpase_activation

Participant: Gene Product: E. coli DnaJ

Gene Product:

E. coli DnaJUniProtKB:P08622

Function

DnaK ATPase activator activityGO:0001671

Substrates: DnaK-ATP bound to a non-native client

Products: DnaK-ADP-client complex phosphate

Processes

protein refoldingGO:0042026

Locations

cytosolGO:0005829

DnaJ captures misfolded clients and stimulates DnaK ATP hydrolysis through its conserved J-domain HPD motif.

Part 2: DnaK ATP-coupled client remodeling

DnaK ATP-dependent client remodelingReactiondnak_client_remodeling

DnaK undergoes ATP-dependent cycles of client binding, hydrolysis-driven clamping, and nucleotide-exchange-triggered release that convert stably misfolded proteins into folding-competent intermediates.

Annotons

DnaK ATP-dependent folding chaperone

dnak_atp_dependent_chaperone

Participant: Gene Product: E. coli DnaK

Gene Product:

E. coli DnaKUniProtKB:P0A6Y8

Function

ATP-dependent protein folding chaperoneGO:0140662

Substrates: ATP misfolded protein client

Products: ADP phosphate DnaK-bound folding intermediate

Processes

protein refoldingGO:0042026

Locations

cytosolGO:0005829

DnaK is the ATP-hydrolyzing Hsp70 core of the bacterial refolding cycle.

Part 3: GrpE nucleotide exchange and DnaK reset

GrpE-catalyzed DnaK nucleotide exchangeReactiongrpe_nucleotide_exchange

The GrpE dimer binds DnaK's nucleotide-binding domain and accelerates ADP release, allowing ATP rebinding, client release, and another DnaK/DnaJ remodeling cycle.

Annotons

GrpE DnaK nucleotide-exchange factor

grpe_nucleotide_exchange_factor

Participant: Gene Product: E. coli GrpE

Gene Product:

E. coli GrpEUniProtKB:P09372

Function

adenyl-nucleotide exchange factor activityGO:0000774

Substrates: ADP-bound DnaK-client complex ATP

Products: ATP-bound DnaK folding-competent protein client ADP

Processes

protein refoldingGO:0042026

Locations

cytosolGO:0005829

GrpE catalyzes nucleotide exchange on DnaK, releasing ADP and allowing ATP rebinding to reset the Hsp70 chaperone cycle.