The three-dimensional structure of human S100A12.
The crystal structure of human EF-hand calcium-binding protein S100A12 in its calcium-bound form has been determined to 1.95 A resolution by molecular replacement using the structure of the S100B protein. The S100 family members are homologous to calmodulin and other related EF-hand calcium-binding proteins. Like the majority of S100 proteins, S100A12 is a dimer, with the interface between the two subunits being composed mostly of hydrophobic residues. The fold of S100A12 is similar to the other known crystal and solution structures of S100 proteins, except for the linker region between the two EF-hand motifs. Sequence and structure comparison between members of the S100 family suggests that the target-binding region in S100A12 is formed by the linker region and C-terminal residues of one subunit and the N-terminal residues of another subunit of the dimer. The N-terminal region of the target-binding site includes two glutamates that are conserved in most of the S100 sequences. The comparison also provided a better understanding of the role of the residues important for intra- and inter-subunit hydrophobic interactions. The precise role of S100A12 in cell behaviour is yet undefined, as is the case for the whole family, although it has been shown that the interaction of S100A12 with the RAGE receptor is implicated in inflammatory response.
Moroz
O V
OV
Structural Biology Laboratory, Department of Chemistry, University of York, York YO10 5DD, England.
Antson
A A
AA
Murshudov
G N
GN
Maitland
N J
NJ
Dodson
G G
GG
Wilson
K S
KS
Skibshøj
I
I
Lukanidin
E M
EM
Bronstein
I B
IB
D000595:Amino Acid Sequence; D002135:Calcium-Binding Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D009418:S100 Proteins; D000067616:S100A12 Protein; D017386:Sequence Homology, Amino Acid
D002135:Calcium-Binding Proteins; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human