| Topic | Key finding | Key quantitative details | Evidence type (biochemistry/NMR/genetics/review/modeling) | Primary source (first author year journal) | URL | Citation ID |
|---|---|---|---|---|---|---|
| Identity | The target matches **hdeB** in *Escherichia coli* K-12: a small acid-protective chaperone encoded with **hdeA** in the **hdeA-hdeB** acid-stress operon; older literature also refers to the Hde system as part of the acid fitness island. | HdeB is reported as a ~10 kDa periplasmic chaperone; HdeA/HdeB share only ~13% sequence identity but similar folds (RMSD ~1.75 Å). | biochemistry, genetics | Dahl 2015 JBC | https://doi.org/10.1074/jbc.m114.612986 | (pqac-00000007, pqac-00000010, pqac-00000014) |
| Localization | HdeB functions in the **periplasm**, where it protects periplasmic proteins from acid-induced aggregation; the periplasm rapidly equilibrates with the external acidic milieu. | Environmental/periplasmic pH can fall to ~1–3 during extreme acid stress; cytoplasmic defenses maintain cytoplasmic pH around ~4.5, emphasizing the need for periplasm-specific chaperones. | review, physiology | Hong 2012 Trends Microbiol | https://doi.org/10.1016/j.tim.2012.03.001 | (pqac-00000006, pqac-00000013) |
| Molecular function | HdeB is an **acid-activated holdase chaperone** that binds unfolding periplasmic proteins, prevents aggregation, and supports refolding after neutralization; it is functionally distinct from HdeA. | HdeB shows negligible activity at pH 2, modest activity at pH 3, and optimal activity at about pH 4–5; overexpression improves growth at pH 4. | biochemistry | Dahl 2015 JBC | https://doi.org/10.1074/jbc.m114.612986 | (pqac-00000001, pqac-00000007, pqac-00000010) |
| Mechanism | Unlike HdeA, HdeB activates **before full monomerization/unfolding**; increased conformational dynamics near mildly acidic pH appear sufficient for chaperone activation while the protein remains largely folded and dimeric. | At neutral pH HdeB is dimeric; monomerization is prominent at pH 2–3, but activation already occurs around pH ~4. | biochemistry, NMR | Dahl 2015 JBC | https://doi.org/10.1074/jbc.m114.612986 | (pqac-00000001, pqac-00000009) |
| Mechanism | NMR/sedimentation analyses support a **dynamic dimer** model for HdeB, with pH-dependent exchanges centered at the dimer interface rather than wholesale unfolding. | Sedimentation coefficient: ~1.5 S at pH 7 (dimer), ~1.9 S at pH 4–5, ~1.2 S at pH 2 (monomer); conformational exchange rates reported around ~2000 s^-1 at neutral pH and ~1000 s^-1 at pH 4.5/4.0. | NMR, biophysics | Ding 2015 Sci Rep | https://doi.org/10.1038/srep16856 | (pqac-00000004) |
| Physiological role | The **hdeAB** system is important for acid survival in enteric bacteria and supports survival under severe acid stress by protecting periplasmic proteins. | Disruption of **hdeAB** severely compromises acid survival; in some non-O157 strains, loss of HdeA/HdeB causes >100- to 1000-fold survival reductions under acid stress. | genetics, review | Hong 2012 Trends Microbiol; Carter 2012 AEM | https://doi.org/10.1016/j.tim.2012.03.001 ; https://doi.org/10.1128/aem.07033-11 | (pqac-00000002, pqac-00000006, pqac-00000014) |
| Strain-specific genetics | In *E. coli* O157:H7, **hdeB** is often effectively silenced by a start-codon mutation, showing that HdeB contribution can vary by lineage; this does **not** apply to the K-12 target protein but helps avoid symbol/function confusion. | In 26 O157:H7 strains examined, the putative start codon changed from **ATG to ATA**; hdeB deletion had no effect in O157:H7, whereas non-O157 strains showed strong dependence on HdeA/HdeB. | genetics | Carter 2012 AEM | https://doi.org/10.1128/aem.07033-11 | (pqac-00000000, pqac-00000014) |
| Regulation | hdeAB is embedded in the broader acid-resistance regulatory network; reviews place **RpoS**, **GadE**, **PhoP**, and the **EvgS/EvgA → YdeO/SafA → PhoQ/PhoP** cascade upstream of hdeAB expression. | No direct fold-change values extracted here, but the pathway logic links RpoS to gadE and gadE/PhoP to hdeAB initiation. | review, regulatory genetics | Zhang 2023 Appl Environ Microbiol | https://doi.org/10.1128/aem.01577-23 | (pqac-00000008, pqac-00000016) |
| Regulation | Earlier genetic work also implicates **H-NS** and the **RcsB/GadE** acid-resistance hierarchy in control of **hdeAB/hdeD**, consistent with placement of hdeB in the acid fitness regulon. | hdeAB/hdeD were identified among H-NS-controlled acid-resistance loci; no specific fold-change values extracted from the evidence snippets. | genetics | Krin 2010 BMC Microbiol | https://doi.org/10.1186/1471-2180-10-273 | (pqac-00000014) |
| Recent understanding (2024) | Recent acid-stress reviews continue to describe HdeA/HdeB as key **periplasmic acid-stress chaperones**, with HdeB emphasized for protection at **milder acidic pH** than HdeA. | 2024 review summarizes HdeB as most active around pH 4, complementing HdeA at stronger acidity. | review | Li 2024 Microorganisms | https://doi.org/10.3390/microorganisms12091774 | (pqac-00000010) |
| Applications / implementations | HdeB is now used conceptually in **acid-tolerance engineering** and **systems models** of *E. coli* stress physiology; integrated models identify periplasmic HdeA/HdeB as major contributors to acid response and useful targets for engineering/health applications. | StressME describes acid-response trade-offs involving cytoplasmic vs periplasmic chaperones and is positioned for engineering and health applications. | modeling | Zhao 2024 PLoS Comput Biol | https://doi.org/10.1371/journal.pcbi.1011865 | (pqac-00000017) |
| Applications / implementations | Industrial strain engineering that activates acid-stress networks can increase acid tolerance and is associated with increased **hdeB** expression/activity, even when not targeting HdeB alone. | DsrA/Hfq engineering improved growth at pH 4.5 by ~51–72% in evolved strains and coincided with activation of AR2 genes and **HdeB**. | engineering, genetics | Lin 2021 Appl Environ Microbiol | https://doi.org/10.1128/AEM.02923-20 | (pqac-00000014) |


*Table: This table summarizes the main functional annotation evidence for E. coli K-12 HdeB (UniProt P0AET2), covering identity, localization, acid-stress chaperone function, activation mechanism, regulation, quantitative observations, and translational relevance. It is useful as a compact evidence map linking major claims to specific sources and context IDs.*