Structure of the human S100A12-copper complex: implications for host-parasite defence.

Area of Science:

• Biochemistry
• Structural Biology
• Immunology

Background:

• S100A12 is a calcium-modulated protein in the S100 family, primarily expressed in granulocytes.
• It is associated with inflammation, allergy, and host-parasite responses.
• S100 protein function is modulated by metals like zinc and copper, not just calcium.

Purpose of the Study:

• To determine the structure of S100A12 in complex with copper.
• To investigate the binding site and stoichiometry of copper interaction with S100A12.
• To understand the implications of copper binding for S100A12 function in the immune system.

Main Methods:

• X-ray crystallography was used to determine the structure of S100A12 bound to copper.
• The crystal structure was refined at 2.19 A resolution in space group P2(1)2(1)2.
• Anomalous difference electron-density maps were calculated using data collected at specific X-ray wavelengths to identify copper binding sites.

Main Results:

• The crystal structure of human S100A12 in complex with copper was determined.
• Each S100A12 monomer binds a single copper ion.
• The copper binding site is analogous to the zinc binding site in the related S100A7 protein.

Conclusions:

• Copper binding is likely essential for the function of S100A12 in the early immune response.
• This highlights a novel metal-dependent mechanism for calgranulin proteins.
• Further research into copper's role in S100A12 and other calgranulins is warranted.