title: Periplasmic protein HdeA exhibits chaperone-like activity exclusively within stomach pH range by transforming into disordered conformation.
abstract: The extremely acidic environment of the mammalian stomach, with a pH range usually between 1 and 3, represents a stressful challenge for enteric pathogenic bacteria such as Escherichia coli before they enter into the intestine. The hdeA gene of E. coli was found to be acid inducible and was revealed by genetic studies to be important for the acid survival of the strain. This study was performed in an attempt to characterize the mechanism of the activity of the HdeA protein. Our data provided in this report strongly suggest that 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). Furthermore, our data indicate that HdeA exposes hydrophobic surfaces that appear to be involved in the binding of denatured substrate proteins at extremely low pH values. In light of our observations, models are proposed to explain the action of HdeA in both a physiological and a molecular context.
authors.affiliation: The National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences and College of Chemistry and Molecular Engineering, Peking University, Beijing 100871.
authors.forename: Weizhe
authors.initials: W
authors.lastname: Hong
authors.forename: Wangwang
authors.initials: W
authors.lastname: Jiao
authors.forename: Jicheng
authors.initials: J
authors.lastname: Hu
authors.forename: Junrui
authors.initials: J
authors.lastname: Zhang
authors.forename: Chong
authors.initials: C
authors.lastname: Liu
authors.forename: Xinmiao
authors.initials: X
authors.lastname: Fu
authors.forename: Dan
authors.initials: D
authors.lastname: Shen
authors.forename: Bin
authors.initials: B
authors.lastname: Xia
authors.forename: Zengyi
authors.initials: Z
authors.lastname: Chang
mesh_terms: D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D018832:Molecular Chaperones; D033903:Periplasmic Proteins; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D013270:Stomach / Q000382:microbiology*
chemical_list: D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; D033903:Periplasmic Proteins; C084501:hdeA protein, E coli