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The structure of Ca 2+ ‐loaded S100A2 at 1.3‐Å resolution
Author(s) -
Koch Michael,
Fritz Günter
Publication year - 2012
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2012.08556.x
Subject(s) - intramolecular force , helix (gastropod) , ef hand , chemistry , protein data bank , crystallography , conformational change , calcium binding protein , biophysics , binding site , protein structure , calcium , stereochemistry , biochemistry , biology , ecology , organic chemistry , snail
S100A2 is an EF‐hand calcium ion (Ca 2+ )‐binding protein that activates the tumour suppressor p53. In order to understand the molecular mechanisms underlying the Ca 2+ ‐induced activation of S100A2, the structure of Ca 2+ ‐bound S100A2 was determined at 1.3 Å resolution by X‐ray crystallography. The structure was compared with Ca 2+ ‐free S100A2 and with other S100 proteins. Binding of Ca 2+ to S100A2 induces small structural changes in the N‐terminal EF‐hand, but a large conformational change in the C‐terminal EF‐hand, reorienting helix III by approximately 90°. This movement is accompanied by the exposure of a hydrophobic cavity between helix III and helix IV that represents the target protein interaction site. This molecular reorganization is associated with the breaking and new formation of intramolecular hydrophobic contacts. The target binding site exhibits unique features; in particular, the hydrophobic cavity is larger than in other Ca 2+ ‐loaded S100 proteins. The structural data underline that the shape and size of the hydrophobic cavity are major determinants for target specificity of S100 proteins and suggest that the binding mode for S100A2 is different from that of other p53‐interacting S100 proteins. Database
Structural data are available in the Protein Data Bank database under the accession number 4DUQ Structured digital abstract• S100A2 and S100A2 bind by x‐ray crystallography ( View interaction )