A Histidine-rich and Cysteine-rich Metal-binding Domain at the C Terminus of Heat Shock Protein A from Helicobacter pylori

Abstract

HspA, a member of the GroES chaperonin family, is a small protein found in Helicobacter pylori with a unique histidineand cysteine-rich domain at the C terminus. In this work, we overexpressed, purified, and characterized this protein both in vitro and in vivo.

Hydrogenase activity in the foodborne pathogen Campylobacter jejuni depends upon a novel ABC-type nickel transporter (NikZYXWV) and is SlyD-independent

“…These include Hpn, an abundant histidine-rich protein (Gilbert et al, 1995;Ge et al, 2006), Hpn2 (Zeng et al, 2008), Mua (Benoit & Maier, 2008) and HspA, an unusual GroES homologue. HspA has a C-terminal extension containing a metal binding domain (Cun et al, 2008) that functions in nickel sequestration and detoxification, and in maturation of hydrogenase (Schauer et al, 2010). The Cterminal extension of HspA is only conserved in and restricted to H. pylori strains and the closely related Helicobacter acinonychis (Schauer et al, 2010).…”

Novel class of Bi(iii) hydroxamato complexes: synthesis, urease inhibitory activity and activity against H. pylori

“…13 Recently innovative metallomic and metalloproteomic approaches have aided identification of Bi targeting proteins in H. pylori such as HspA, Ef-Tu, NapA and urease (UreA and UreB) and revealed that Bi(III) has a high selectivity for cysteines and histidines, particularly motif patterns of CX n C, CX n H and HX n H. Evidence therefore suggests that Bi interference with metal homeostasis and oxidation reduction processes may be important. [14][15][16][17][18] Significantly it was recently demonstrated that glutathione and multidrug resistance protein transporter remove Bi from human cells, thereby protecting the human body from associated toxicity and also providing a level of selectivity between human cells and bacterial cells that lack glutathione such as H. pylori.…”

The C-Terminal Disulfide Bonds of Helicobacter pylori GroES Are Critical for IL-8 Secretion via the TLR4-Dependent Pathway in Gastric Epithelial Cells

“…Domain B consists of 28 aa, including 8 histidine and 4 cysteine residues, with the latter forming two disulfide bonds, C94-C111 and C95-C112, generating a closed-loop structure (27). Apart from its cochaperone activity, HpGroES plays important roles in nickel homeostasis and urease activation (25,28,29). Besides these roles in intracellular locations (30), HpGroES is able to gain access to the extracellular compartment and is highly antigenic (29,31) and is specifically recognized by serum Abs in H. pylori-infected patients and is considered a potential candidate for vaccine development and diagnosis of H. pylori infection (32,33).…”

“…In addition to the highly conserved GroES chaperonin domain, named domain A, HpGroES contains a C-terminal extension domain named domain B (residues 91-118), which is absent in the other GroES members (25). Domain B consists of 28 aa, including 8 histidine and 4 cysteine residues, with the latter forming two disulfide bonds, C94-C111 and C95-C112, generating a closed-loop structure (27).…”

“…HpGroES, also referred to as heat shock protein (HSP) A, is an unusual homolog of the essential bacterial GroES chaperonin family (25), the members of which serve as cochaperonins of the heptameric GroEL/GroES barrel complex, which mediates the refolding of a variety of nonnative proteins (26). In addition to the highly conserved GroES chaperonin domain, named domain A, HpGroES contains a C-terminal extension domain named domain B (residues 91-118), which is absent in the other GroES members (25).…”