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Expression, Purification, and Antimicrobial Activity of S100A12
Published on: May 13, 2017
Multiple structural states of S100A12: A key to its functional diversity
O V Moroz1, G G Dodson, K S Wilson
1Structural Biology Laboratory, Department of Chemistry, University of York, York, YO10 5DD, United Kingdom YO10 5YW.
Microscopy Research and Technique
|March 20, 2003
Summary
S100A12 protein, involved in inflammation and host-parasite defense, binds copper. This interaction may generate reactive oxygen species, contributing to its function in immune responses.
Area of Science:
- Biochemistry
- Immunology
- Structural Biology
Background:
- S100A12 is an EF-hand calcium-binding protein within the S100 family, primarily found in human granulocytes.
- It plays a role in host-parasite interactions and is implicated in autoimmune diseases, particularly those linked to filarial parasites.
- S100A12 interacts with the receptor for advanced glycation end products (RAGE), mediating inflammatory processes.
Purpose of the Study:
- To elucidate the structural characteristics and functional mechanisms of S100A12.
- To investigate the potential role of copper binding in S100A12 function.
- To explore S100A12's involvement in host-parasite responses and inflammation.
Main Methods:
- X-ray crystallography was employed to determine the structure of S100A12 in two crystal forms (R3 and P2(1)).
- Analysis of copper binding at a specific site on the protein surface.
- Investigation of S100A12's role in neuritogenesis and interaction with RAGE.
Main Results:
- S100A12 forms dimers in the R3 crystal form and hexamers in the P2(1) crystal form, suggesting a role in receptor oligomerization.
- The protein binds copper at a surface-accessible site.
- Recombinant S100A12 demonstrated the ability to induce neuritogenesis in cultured hippocampal cells.
Conclusions:
- The hexameric structure of S100A12 suggests a role in receptor oligomerization.
- Copper binding to S100A12 may facilitate the generation of reactive oxygen species, contributing to its function in host-parasite defense.
- S100A12 exhibits neuritogenic properties and interacts with RAGE, highlighting its multifaceted roles in cellular processes and immunity.
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