E. coli HdeA/HdeB periplasmic acid-stress holdases

A periplasmic acid-stress module in which the ATP-independent chaperones HdeA and HdeB bind acid-unfolding client proteins, suppress irreversible aggregation, and preserve them for refolding after neutralization. HdeA is activated under extreme acid through dimer dissociation and disordering, whereas HdeB acts at milder acidic pH through a distinct dynamic folded-dimer mechanism. HdeB also supports client refolding after neutralization, but the direct release step has not yet been separated from potential downstream folding factors. Acid-sensing transcriptional regulation, cytoplasmic pH homeostasis, HdeB-specific post-neutralization handoff, and the post-neutralization cooperation of DegP and SurA are outside this focused in-situ holdase module.

MODULE:enterobacterial_acid_stress_holdasesDRAFTCONCRETEBiological Processmodules/enterobacterial_acid_stress_holdases.yaml
cellular stress response to acidic pHGO:1990451 protein stabilizationGO:0050821
GO:1990451
cellular stress response to acidic pH
Defines the stress-response process served by HdeA and HdeB.
GO:0050821
protein stabilization
Captures HdeA/HdeB prevention of irreversible periplasmic protein aggregation during acid stress.
file:genes/ECOLI/HdeA/HdeA-ai-review.yaml
ECOLI HdeA gene review
The completed E. coli HdeA review grounds HdeA as a pH-below-3 acid-activated in-situ holdase and refolding chaperone.
file:genes/ECOLI/HdeB/HdeB-ai-review.yaml
ECOLI HdeB gene review
The completed E. coli HdeB review grounds HdeB as a mildly acidic-pH in-situ holdase.
PMID:10623550
HDEA, a periplasmic protein that supports acid resistance in pathogenic enteric bacteria.
Establishes HdeA acid-stress protection and suppression of aggregation by acid-denatured proteins.
PMID:15911614
Periplasmic protein HdeA exhibits chaperone-like activity exclusively within stomach pH range by transforming into disordered conformation.
Establishes the low-pH conformational switch that activates HdeA client binding.
PMID:20080625
Protein refolding by pH-triggered chaperone binding and release.
Establishes that HdeA can facilitate refolding after pH neutralization through a slow client-release cycle.
PMID:17085547
Escherichia coli HdeB is an acid stress chaperone.
Establishes HdeB as an acid-stress chaperone that prevents periplasmic-protein aggregation at acidic pH.
PMID:25391835
HdeB functions as an acid-protective chaperone in bacteria.
Refines HdeB as an acid-protective holdase with an activity optimum distinct from HdeA and shows that HdeB can support client refolding after neutralization.
PMID:26593705
HdeB chaperone activity is coupled to its intrinsic dynamic properties.
Establishes that HdeB activation is coupled to intrinsic dynamics rather than the HdeA-like global unfolding switch.
file:projects/UNFOLDED_PROTEIN_BINDING.md
Unfolded protein binding annotation review project
Records the ontology boundary: GO:0051082 is obsolete, GO:0140309 is carrier-specific, and in-situ holdases need a general holdase chaperone activity term.

HdeA and HdeB are modeled as in-situ acid holdases rather than OMP carrier-holdases. Their reviewed core functions use a proposed holdase chaperone activity because no current GO molecular-function term exactly captures local aggregation prevention without escort to a defined acceptor.

4Nodes
3Parts
0Variant Sets
0Variants
3Annotons
1Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:enterobacterial_acid_stress_holdases 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

1 gene-function check(s) reflected in core functions · 0 conflict(s) · 2 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.

AnnotonParticipantFunctionAssessment
hdea_holdase E. coli HdeA
UniProtKB:P0AES9
Gene 		holdase chaperone activity
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
hdeb_holdase E. coli HdeB
UniProtKB:P0AET2
Gene 		holdase chaperone activity
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
hdea_refolding_chaperone E. coli HdeA
UniProtKB:P0AES9
Gene 		protein folding chaperone
GO:0044183 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).

Gene-review completeness (2/2 grounded genes reviewed)

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

Gene Review Complete Deep research
HdeA P0AES9 ✓ ✓ ✓
HdeB P0AET2 ✓ ✓ ✓

Details

Context
Escherichia coli K-12NCBITaxon:83333
E. coli HdeA/HdeB periplasmic acid-stress holdasesBiological Processenterobacterial_acid_stress_holdases
cellular stress response to acidic pHGO:1990451 protein stabilizationGO:0050821
Context
Escherichia coli K-12NCBITaxon:83333

Connections

HdeA-bound soluble clients generated during extreme acid stress become substrates for HdeA's slow neutralization-triggered release/refolding cycle.
Part 1: extreme-acid HdeA holdase protection
HdeA extreme-acid holdase protectionBiological Processhdea_extreme_acid_holdase

Annotons

HdeA acid-activated holdase
hdea_holdase
Participant: Gene Product: E. coli HdeA
Gene Product:
E. coli HdeAUniProtKB:P0AES9

Function

holdase chaperone activity
Substrates: acid-denatured periplasmic protein
Products: soluble HdeA-bound unfolded periplasmic protein

Processes

cellular stress response to acidic pHGO:1990451 protein stabilizationGO:0050821

Locations

outer membrane-bounded periplasmic spaceGO:0030288

Disordered acid-activated monomer that binds acid-denatured clients below pH 3 and suppresses irreversible aggregation.

Part 2: mildly acidic HdeB holdase protection
HdeB mild-acid holdase protectionBiological Processhdeb_mild_acid_holdase

Annotons

HdeB acid-activated holdase
hdeb_holdase
Participant: Gene Product: E. coli HdeB
Gene Product:
E. coli HdeBUniProtKB:P0AET2

Function

holdase chaperone activity
Substrates: acid-unfolding periplasmic protein
Products: soluble HdeB-bound unfolded periplasmic protein

Processes

cellular stress response to acidic pHGO:1990451 protein stabilizationGO:0050821

Locations

outer membrane-bounded periplasmic spaceGO:0030288

Folded and dynamic acid-activated holdase that protects periplasmic clients at milder acidic pH than HdeA.

Part 3: pH-neutralization refolding
HdeA-assisted refolding after neutralizationBiological Processhdea_client_refolding_release

Annotons

HdeA pH-triggered refolding chaperone
hdea_refolding_chaperone
Participant: Gene Product: E. coli HdeA
Gene Product:
E. coli HdeAUniProtKB:P0AES9

Function

protein folding chaperoneGO:0044183
Substrates: HdeA-bound acid-denatured client protein
Products: refolding-competent released client protein

Processes

protein refoldingGO:0042026

Locations

outer membrane-bounded periplasmic spaceGO:0030288

Slow client release after neutralization assists HdeA-bound acid-denatured proteins in returning to the folding pathway.