Structure of the human S100A12-copper complex: implications for host-parasite defence.
S100A12 is a member of the S100 family of EF-hand calcium-modulated proteins. Together with S100A8 and S100A9, it belongs to the calgranulin subfamily, i.e. it is mainly expressed in granulocytes, although there is an increasing body of evidence of expression in keratinocytes and psoriatic lesions. As well as being linked to inflammation, allergy and neuritogenesis, S100A12 is involved in host-parasite response, as are the other two calgranulins. Recent data suggest that the function of the S100-family proteins is modulated not only by calcium, but also by other metals such as zinc and copper. Previously, the structure of human S100A12 in low-calcium and high-calcium structural forms, crystallized in space groups R3 and P2(1), respectively, has been reported. Here, the structure of S100A12 in complex with copper (space group P2(1)2(1)2; unit-cell parameters a = 70.6, b = 119.0, c = 90.2 A) refined at 2.19 A resolution is reported. Comparison of anomalous difference electron-density maps calculated with data collected with radiation of wavelengths 1.37 and 1.65 A shows that each monomer binds a single copper ion. The copper binds at an equivalent site to that at which another S100 protein, S100A7, binds zinc. The results suggest that copper binding may be essential for the functional role of S100A12 and probably the other calgranulins in the early immune response.
Moroz
O V
OV
Department of Chemistry, University of York, York YO10 5YW, England. olga@ysbl.york.ac.uk
Antson
A A
AA
Grist
S J
SJ
Maitland
N J
NJ
Dodson
G G
GG
Wilson
K S
KS
Lukanidin
E
E
Bronstein
I B
IB
D000595:Amino Acid Sequence; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D003460:Crystallization; D018360:Crystallography, X-Ray; D020832:EF Hand Motifs; D006790:Host-Parasite Interactions; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D009418:S100 Proteins / Q000737:chemistry* / Q000378:metabolism; D000067616:S100A12 Protein; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D015032:Zinc / Q000737:chemistry / Q000378:metabolism
D011994:Recombinant Proteins; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human; D003300:Copper; D015032:Zinc; D002118:Calcium