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The solution structure of the bovine S100B protein dimer in the calcium-free state.

Kilby PM, Van Eldik LJ, Roberts GC
Structure 4 1041-52 (1996)
Cited: 73 times
EuropePMC logo PMID: 8805590

Abstract

Background

S100B (S100beta) is a member of the S100 family of small calcium-binding proteins: members of this family contain two helix-loop-helix calcium-binding motifs and interact with a wide range of proteins involved mainly in the cytoskeleton and cell proliferation. S100B is a neurite-extension factor and levels of S100B are elevated in the brains of patients with Alzheimer's disease or Down's syndrome: the pattern of S100B overexpression in Alzheimer's disease correlates with the pattern of neuritic-plaque formation. Identification of a growing class of S100 proteins and the likely neurochemical importance of S100B make the determination of the structure of S100B of interest.

Results

We have used NMR to determine the structure of the reduced S100B homodimer in the absence of calcium. Each monomer consists of a four-helix bundle, arranged in the dimer in an antiparallel fashion. The fourth helix of each monomer runs close to the equivalent helix of the other monomer for almost its full length, extending the hydrophobic core through the interface. The N-terminal, but not the C-terminal, calcium-binding loop is similar to the equivalent loop in the monomeric S100 protein calbindin and is in a conformation ready to bind calcium.

Conclusion

The novel dimer structure reported previously for calcyclin (S100A6) is the common fold for the dimeric S100B proteins. Calcium binding to the C-terminal calcium-binding loop would be expected to require a conformational change, which might provide a signal for activation. The structure suggests regions of the molecule likely to be involved in interactions with effector molecules.

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Reviews citing this publication (13)

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Articles citing this publication (57)

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  23. Unmasking the annexin I interaction from the structure of Apo-S100A11. Dempsey AC, Walsh MP, Shaw GS. Structure 11 887-897 (2003)
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  25. The effects of CapZ peptide (TRTK-12) binding to S100B-Ca2+ as examined by NMR and X-ray crystallography. Charpentier TH, Thompson LE, Liriano MA, Varney KM, Wilder PT, Pozharski E, Toth EA, Weber DJ. J Mol Biol 396 1227-1243 (2010)
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  55. Computational Design of Macrocyclic Binders of S100B(ββ): Novel Peptide Theranostics. Kannan S, Aronica PGA, Nguyen TB, Li J, Verma CS. Molecules 26 (2021)
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