Gene Ontology annotation through association of InterPro records with GO terms

Electronic Gene Ontology annotations created by transferring manual GO annotations between related proteins based on shared sequence features

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:17085547

Escherichia coli HdeB is an acid stress chaperone.

HdeB is a periplasmic acid stress chaperone
HdeB is more effective than HdeA at pH 3
Both HdeA and HdeB are required for optimal acid stress protection
HdeB dissociates from dimers to monomers at acidic pH

PMID:25391835

HdeB functions as an acid-protective chaperone in bacteria.

HdeB chaperone function is optimal at pH 4, where it remains fully dimeric and largely folded, in contrast to HdeA which is optimal at pH 2 via monomerization and partial unfolding.

"in contrast to HdeA, whose chaperone function is optimal at pH 2, the chaperone function of HdeB is optimal at pH 4, at which HdeB is still fully dimeric and largely folded."
The highly dynamic nature of HdeB at pH 4 alleviates the need for monomerization and partial unfolding for chaperone activation.

"the highly dynamic nature of HdeB at pH 4 alleviates the need for monomerization and partial unfolding."
Once activated, HdeB binds unfolding client proteins, prevents their aggregation, and supports their refolding upon neutralization.

"Once activated, HdeB binds various unfolding client proteins, prevents their aggregation, and supports their refolding upon subsequent neutralization."

PMID:26593705

HdeB chaperone activity is coupled to its intrinsic dynamic properties.

HdeB has a higher optimal activation pH (pH 4-5) than HdeA, and under these conditions maintains a well-folded dimer.

"HdeB appears to have a much higher optimal activation pH (pH 4-5), under which condition the protein maintains a well-folded dimer"
HdeB activation is coupled to its intrinsic dynamics rather than to structural changes, distinguishing its mechanism from HdeA.

"HdeB activation is coupled to its intrinsic dynamics instead of structural changes, and therefore its functional mechanism is apparently different from HdeA."

PMID:22138344

Salt bridges regulate both dimer formation and monomeric flexibility in HdeB and may have a role in periplasmic chaperone function.

Structural basis for HdeB dimerization and monomer flexibility

file:ECOLI/HdeB/HdeB-deep-research-falcon.md

Falcon (Edison Scientific) deep research report on E. coli HdeB (P0AET2)

HdeB is an acid-activated, ATP-independent holdase chaperone that binds unfolding periplasmic proteins, prevents their irreversible aggregation, and supports refolding during neutralization.

"**HdeB** is an **acid-activated, ATP-independent “holdase” chaperone** in the periplasm. Its primary function is to **bind unfolding periplasmic proteins under acidic conditions**, prevent their **irreversible aggregation**, and support **refolding during neutralization**"
HdeB is optimally active at mildly acidic pH (~4), with negligible activity at pH 2 and only modest activity at pH 3, complementing HdeA which acts at stronger acidity.

"In vitro, HdeB shows **negligible activity at pH 2**, **modest activity at pH 3**, and **optimal activity near pH ~4**; correspondingly, overexpression phenotypes show that **HdeB supports growth/survival at pH ~4**"
Unlike HdeA, HdeB activation precedes acid-induced monomerization; increased conformational flexibility at mildly acidic pH activates chaperone function while the protein remains largely folded and dimeric.

"In contrast, **HdeB activation “precedes” acid-induced monomerization**, indicating that activity at mild acidity is not simply caused by dimer breakup and global unfolding. Instead, HdeB appears to become chaperone-active via **increased flexibility/local rearrangements** at mildly acidic pH while remaining largely folded and dimeric."
NMR and sedimentation data support a dynamic dimer model, with sedimentation coefficients shifting with pH (dimeric ~1.5 S at pH 7, ~1.9 S at pH 4-5, monomeric ~1.2 S at pH 2).

"NMR/biophysical data support a **dynamic dimer** model: HdeB remains dimeric at neutral pH (sedimentation ~1.5 S), is monomeric at very low pH (~1.2 S at pH 2), and shows altered sedimentation behavior at pH 4–5 (~1.9 S)."
HdeB functions in the periplasm, protecting periplasmic proteins from acid-induced aggregation as the periplasm rapidly equilibrates with the external acidic environment.

"HdeB functions in the **periplasm**, where it protects periplasmic proteins from acid-induced aggregation; the periplasm rapidly equilibrates with the external acidic milieu."
Loss of both HdeA and HdeB severely compromises acid survival, with >100- to 1000-fold survival reductions reported under acid stress in some non-O157 strains.

"loss of HdeA/HdeB causes >100- to 1000-fold survival reductions under acid stress"

file:projects/UNFOLDED_PROTEIN_BINDING.md

Unfolded protein binding annotation review project

GO:0051082 is obsolete; GO:0140309 is carrier-specific and requires escort to a defined acceptor or location; acid-activated in-situ holdases require the proposed general holdase chaperone activity term.