title: Protein refolding by pH-triggered chaperone binding and release.
abstract: Molecular chaperones are typically either adenosine triphosphate (ATP) dependent or rely heavily on their ATP-dependent chaperone counterparts in order to promote protein folding. This presents a challenge to chaperones that are localized to ATP-deficient cellular compartments. Here we describe a mechanism by which the pH-regulated acid stress chaperone HdeA is capable of independently facilitating the refolding of acid-denatured proteins in the bacterial periplasm, which lacks both ATP and ATP-dependent chaperone machines. Our results are consistent with a model in which 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. Unlike previously characterized chaperones, HdeA appears to facilitate protein folding by using a single substrate binding-release cycle. This cycle is entirely regulated by the external environment and is therefore energy-neutral for the bacteria.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Tapley
authors.forename: Titus M
authors.initials: TM
authors.lastname: Franzmann
authors.forename: Sumita
authors.initials: S
authors.lastname: Chakraborty
authors.forename: Ursula
authors.initials: U
authors.lastname: Jakob
authors.forename: James C A
authors.initials: JC
authors.lastname: Bardwell
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D018832:Molecular Chaperones / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding
chemical_list: D018832:Molecular Chaperones; D000255:Adenosine Triphosphate