Multiple structural states of S100A12: A key to its functional diversity.
S100A12 is a member of the S100 family of EF-hand calcium-binding proteins. Together with two other calgranulins, S100A8 and S100A9, it is mostly expressed in human granulocytes, although there is increasing evidence of expression in keratinocytes and psoriatic lesions. It is involved in host-parasite response, and linked to corneal autoimmune diseases connected with filarial parasite infestation. Interaction of S100A12 with a multiligand receptor for advanced glycation end products (RAGE) mediates inflammation. Human recombinant S100A12 was found to induce neuritogenesis of cultured hippocampal cells, similar to two other S100 proteins, S100B and S100A4. X-ray structure of S100A12 has been solved in two crystal forms: R3 and P2(1). In the R3 crystal form S100A12 is a dimer, and in the P2(1) crystal form the dimers are arranged as a hexamer. The hexameric form suggests its role in receptor oligomerisation. S100A12 binds copper at the predicted zinc/copper binding site, which is located close to the surface of the protein. We propose copper-mediated generation of reactive oxygen species by S100A12 as its function in host-parasite response.
Moroz
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Structural Biology Laboratory, Department of Chemistry, University of York, York, YO10 5DD, United Kingdom YO10 5YW.
Dodson
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Wilson
K S
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Lukanidin
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Bronstein
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D000595:Amino Acid Sequence; D000818:Animals; D003300:Copper / Q000378:metabolism*; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D006790:Host-Parasite Interactions; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010272:Parasitic Diseases / Q000276:immunology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins / Q000737:chemistry* / Q000378:metabolism*; D000067616:S100A12 Protein
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human; D003300:Copper