Heat shock protein A (HspA) (HspA)

Heat shock protein A (HspA) is a specialized GroES-like co-chaperonin found in the gastric pathogen Helicobacter pylori (UniProt P0A0S4). Unlike standard GroES proteins, HspA possesses a unique C-terminal extension rich in histidine and cysteine residues, which allows it to bind nickel ions (PubMed 20061471). This dual functionality enables HspA to assist in protein folding as a co-chaperonin for GroEL (HspB) while simultaneously acting as a nickel chaperone (PubMed 40507876). Nickel sequestration by HspA is vital for the maturation of enzymes like hydrogenase and potentially urease, which are essential for the bacterium's survival in the acidic stomach environment (PubMed 20061471). HspA also plays a role in the bacterial stress response and adhesion to host gastric epithelial cells. Due to its essentiality and surface exposure, HspA is a prominent candidate for the development of H. pylori vaccines (PubMed 12702543). Furthermore, it is a known target for bismuth-based drugs, which bind to its C-terminal tail and disrupt nickel homeostasis (Chem. Commun. 2015, 51, 16479). Inhibition of HspA leads to impaired bacterial colonization and reduced pathogenicity.

Other names

GroES homolog10 kDa chaperoninCpn10Nickel-binding protein

Bismuth-mediated inhibition of nickel binding and sequestration; disruption of co-chaperonin activity in protein folding; antigenic stimulation for vaccine-induced immunity.