"it is a small (~11 kDa) ATP-independent holdase that prevents acid-denatured **periplasmic proteins** from aggregating and assists refolding after pH neutralization. It is inactive as a folded dimer at neutral pH and active in acid as a partially unfolded monomer/disordered state."

"it is **inactive when folded** and becomes **active when partially unfolded/disordered** under acid stress."

"HdeA prevents irreversible aggregation while pH is low, and clients can refold upon neutralization when HdeA releases them."

"HdeA operates in the **periplasm**, where it interacts with periplasmic proteins that are prone to acid denaturation/aggregation when external pH drops."

"HdeA undergoes **dimer-to-monomer transition** plus **partial unfolding/order-to-disorder conversion**, exposing hydrophobic client-binding patches."

"loss of hdeA decreases survival/viability"

"Best-supported primary role is **protein quality control in the acidic periplasm**, not catalysis or transport."

"The genes coding for the other two proteins, 10K-L and 10K-S, are located at 77.5 min on the genetic map. Their nucleotide sequences were determined"

"We identified several highly abundant proteins, YjbJ, YjbP, YggX, HdeA, and AhpC, which would not have been predicted from the genomic sequence alone ...Our data suggest that AhpC, CspC, and HdeA exist as covalent homomultimers"

"HDEA is activated by a dimer-to-monomer transition at acidic pH, leading to suppression of aggregation by acid-denatured proteins. We suggest that HDEA may support chaperone-like functions during the extremely acidic conditions"

"HdeA employs a novel strategy to modulate its chaperone activity: it possesses an ordered conformation that is unable to bind denatured substrate proteins under normal physiological conditions (i.e. at neutral pH) and transforms into a globally disordered conformation that is able to bind substrate proteins under stress conditions (i.e. at a pH below 3)"

"both proteins are required for optimal protection of the bacterial periplasm against acid stress...At pH 2, the aggregation of periplasmic extracts is prevented by the addition of HdeA...At pH 3, however, HdeB is more efficient than HdeA in preventing periplasmic-protein aggregation"

"HdeA and HdeB not only help to maintain proteins in a soluble state during acid treatment, as previously reported, but also assist, both in vitro and in vivo, in the solubilization at neutral pH of mixed protein-chaperone aggregates formed at acidic pH"

"HdeA stably binds substrates at low pH, thereby preventing their irreversible aggregation. pH neutralization subsequently triggers the slow release of substrate proteins from HdeA, keeping the concentration of aggregation-sensitive intermediates below the threshold where they begin to aggregate. This provides a straightforward and ATP-independent mechanism that allows HdeA to facilitate protein refolding"

"the periplasmic chaperones DegP and SurA were initially found to be protected by HdeA at a low pH, but they subsequently facilitated the HdeA-mediated acid recovery of other client proteins. This unique, ATP-independent chaperone cooperation in the ATP-deprived E. coli periplasm may support the acid resistance of enteric bacteria"

"the structure of activated HdeA becomes largely disordered and exposes two hydrophobic patches essential for client interactions...we identified three acid-sensitive regions that act as structural locks in regulating the exposure of the two client-binding sites during the activation process, revealing a multistep activation mechanism"

"PROTEIN SEQUENCE OF 22-33."

"ECO:0000269|PubMed:9298646,"

"X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), AND DISULFIDE BOND."

"ECO:0000269|PubMed:9731767""