9LL2

Crystal structure of the Helicobacter pylori copper resistance determinant CrdA in the apo form

Summary for 9LL2

• Entry DOI: 10.2210/pdb9ll2/pdb
• Descriptor: Copper resistance protein, SULFATE ION (3 entities in total)
• Functional Keywords: crda, copper ion, metal binding protein
• Biological source: Helicobacter pylori
• Total number of polymer chains: 2
• Total formula weight: 24836.71

Authors

Ki, D.W.,Oh, H.B.,Cho, H.Y.,Song, W.S.,Yoon, S.I. (deposition date: 2025-01-17, release date: 2025-11-19)

Primary citation

Ki, D.U.,Oh, H.B.,Cho, H.Y.,Song, W.S.,Yoon, S.I.
Structural basis of Cu(I) ion recognition by the Helicobacter pylori copper resistance determinant CrdA.
Febs J., 2025

PubMed Abstract: Helicobacter pylori is a bacterium that colonizes the stomach and causes gastric disorders in humans. For successful colonization in the harsh gastric environment, H. pylori employs various homeostatic mechanisms in response to environmental factors, such as protons and copper ions. Copper levels should be maintained below toxicity in the cell while remaining above the threshold required for biological functions. Copper resistance determinant A (CrdA) is a putative copper chaperone protein that contributes to copper homeostasis in H. pylori. To provide insight into CrdA-mediated copper homeostasis, we analyzed the interaction of CrdA with Cu(I) or Cu(II) ions through biochemical and mutational studies and determined the crystal structures of CrdA alone and in complex with a Cu(I) mimic, Ag(I). CrdA exhibited a binding preference for Cu(I) and Ag(I) ions over Cu(II) ions. CrdA forms a Greek key β-barrel structure with a unique protruding methionine-rich motif whose methionine residues coordinate two Ag(I) ions. In particular, the CrdA residue M69 plays a key role in Cu(I) recognition, even at the low pH found in the stomach where H. pylori resides. Furthermore, our structure-based comparative analysis suggests that CrdA has evolved a unique Cu(I) recognition mechanism that has not been observed for other Cu(I) chaperone proteins. Our findings on the specific interaction of CrdA with Cu(I) ions would provide a new avenue for developing H. pylori-targeting antibacterial drugs.

PubMed: 41147750
DOI: 10.1111/febs.70305

Experimental method

X-RAY DIFFRACTION (1.64 Å)