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Analysis of the structure of human apo‐S100B at low temperature indicates a unimodal conformational distribution is adopted by calcium‐free S100 proteins
Author(s) -
Malik Shahid,
Revington Matthew,
Smith Steven P.,
Shaw Gary S.
Publication year - 2008
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22037
Subject(s) - calcium , chemistry , helix (gastropod) , calcium binding protein , crystallography , biophysics , protein structure , biochemistry , biology , ecology , organic chemistry , snail
S100B is one of the best‐characterized members of the calcium‐signaling S100 protein family. Most S100 proteins are dimeric, with each monomer containing two EF‐hand calcium‐binding sites (EF1, EF2). S100B and other S100 proteins respond to calcium increases in the cell by coordinating calcium and undergoing a conformational change that allows them to interact with a variety of cellular targets. Although several three dimensional structures of S100 proteins are available in the calcium‐free (apo‐) state it has been observed that these structures appear to adopt a wide range of conformations in the EF2 site with respect to the positioning of helix III, the helix that undergoes the most dramatic calcium‐induced conformational change. In this work, we have determined the structure of human apo‐S100B at 10°C to examine whether temperature might be responsible for these structural differences. Further, we have used this data, and other available apo‐S100 structures, to show that despite the range of interhelical angles adopted in the apo‐S100 structures, normal Gaussian distributions about the mean angles found in the structure of human apo‐S100B are observed. This finding, only obvious from the analysis of all available apo‐S100 proteins, provides direct structural evidence that helix III is a loosely packed helix. This is likely a necessary functional property of the S100 proteins that facilitates the calcium‐induced conformational change of helix III. In contrast, the calcium‐bound structures of the S100 proteins show significantly smaller variability in the interhelical angles. This shows that calcium binding to the S100 proteins causes not only a conformational change but results in a tighter distribution of helices within the EF2 calcium binding site required for target protein interactions. Proteins 2008. © 2008 Wiley‐Liss, Inc.