Human S100b Protein: Formation of a Tetramer from Synthetic Calcium-binding Site Peptides

Overview

Journal Protein Sci

Specialty Biochemistry

Date 1995 Apr 1

PMID 7613474

Citations 7

Authors

C Donaldson

K R Barber

C M Kay

G S Shaw

Affiliations

Soon will be listed here.

Abstract

Human brain S100b protein is a unique calcium-binding protein comprised of two identical 91-amino acid polypeptide chains that each contain two proposed helix-loop-helix (EF-hand) calcium-binding sites. In order to probe the assembly of the four calcium-binding sites in S100b, a peptide comprised of the N-terminal 46 residues of S100b protein was synthesized and studied by CD and 1H NMR spectroscopies as a function of concentration and temperature. At relatively high peptide concentrations and in the absence of calcium, the peptide exhibited a significant proportion of alpha-helix (45%). Decreasing the peptide concentration led to a loss of alpha-helix as monitored by CD spectroscopy and coincident changes in the 1H NMR spectrum. These changes were also observed by 1H NMR spectroscopy as a function of temperature where it was observed that the Tm of the peptide was lowered approximately 14 degrees C with a 17-fold decrease in peptide concentration. Sedimentation equilibrium studies were used to determine that the peptide formed a tetramer in solution in the absence of calcium. It is proposed that this tetrameric fold also occurs in S100b and is a result of the interaction of portions of all four calcium-binding sites.

Citing Articles

Multilimbed membrane guanylate cyclase signaling system, evolutionary ladder.

Duda T, Sharma R Front Mol Neurosci. 2023; 15:1022771.

PMID: 36683846 PMC: 9849996. DOI: 10.3389/fnmol.2022.1022771.

Targeting S100B Protein as a Surrogate Biomarker and its Role in Various Neurological Disorders.

Langeh U, Singh S Curr Neuropharmacol. 2020; 19(2):265-277.

PMID: 32727332 PMC: 8033985. DOI: 10.2174/1570159X18666200729100427.

Intravitreal S100B Injection Triggers a Time-Dependent Microglia Response in a Pro-Inflammatory Manner in Retina and Optic Nerve.

Grotegut P, Kuehn S, Meissner W, Dick H, Joachim S Mol Neurobiol. 2019; 57(2):1186-1202.

PMID: 31705442 DOI: 10.1007/s12035-019-01786-4.

Intravitreal S100B Injection Leads to Progressive Glaucoma Like Damage in Retina and Optic Nerve.

Kuehn S, Meissner W, Grotegut P, Theiss C, Dick H, Joachim S Front Cell Neurosci. 2018; 12:312.

PMID: 30319357 PMC: 6169322. DOI: 10.3389/fncel.2018.00312.

Integrative Signaling Networks of Membrane Guanylate Cyclases: Biochemistry and Physiology.

Sharma R, Duda T, Makino C Front Mol Neurosci. 2016; 9:83.

PMID: 27695398 PMC: 5023690. DOI: 10.3389/fnmol.2016.00083.

References

Baudier J, Gerard D . Ions binding to S100 proteins: structural changes induced by calcium and zinc on S100a and S100b proteins. Biochemistry. 1983; 22(14):3360-9. DOI: 10.1021/bi00283a009. View

De Francesco R, Pastore A, Vecchio G, Cortese R . Circular dichroism study on the conformational stability of the dimerization domain of transcription factor LFB1. Biochemistry. 1991; 30(1):143-7. DOI: 10.1021/bi00215a021. View

Baudier J, Gerard D . Ions binding to S100 proteins. II. Conformational studies and calcium-induced conformational changes in S100 alpha alpha protein: the effect of acidic pH and calcium incubation on subunit exchange in S100a (alpha beta) protein. J Biol Chem. 1986; 261(18):8204-12. View

Szebenyi D, Moffat K . The refined structure of vitamin D-dependent calcium-binding protein from bovine intestine. Molecular details, ion binding, and implications for the structure of other calcium-binding proteins. J Biol Chem. 1986; 261(19):8761-77. View

Baudier J, Glasser N, Duportail G . Bimane- and acrylodan-labeled S100 proteins. Role of cysteines-85 alpha and -84 beta in the conformation and calcium binding properties of S100 alpha alpha and S100b (beta beta) proteins. Biochemistry. 1986; 25(22):6934-41. DOI: 10.1021/bi00370a029. View

Linse S, Brodin P, Drakenberg T, Thulin E, Sellers P, Elmden K . Structure-function relationships in EF-hand Ca2+-binding proteins. Protein engineering and biophysical studies of calbindin D9k. Biochemistry. 1987; 26(21):6723-35. DOI: 10.1021/bi00395a023. View

GREENFIELD N, Fasman G . Computed circular dichroism spectra for the evaluation of protein conformation. Biochemistry. 1969; 8(10):4108-16. DOI: 10.1021/bi00838a031. View

Kretsinger R, Nockolds C . Carp muscle calcium-binding protein. II. Structure determination and general description. J Biol Chem. 1973; 248(9):3313-26. View

Reid R, Gariepy J, Saund A, Hodges R . Calcium-induced protein folding. Structure-affinity relationships in synthetic analogs of the helix-loop-helix calcium binding unit. J Biol Chem. 1981; 256(6):2742-51. View

10.

Isobe T, Ishioka N, Okuyama T . Structural relation of two S-100 proteins in bovine brain; subunit composition of S-100a protein. Eur J Biochem. 1981; 115(3):469-74. DOI: 10.1111/j.1432-1033.1981.tb06225.x. View

11.

Isobe T, Okuyama T . The amino-acid sequence of the alpha subunit in bovine brain S-100a protein. Eur J Biochem. 1981; 116(1):79-86. DOI: 10.1111/j.1432-1033.1981.tb05303.x. View

12.

Mani R, Shelling J, Sykes B, Kay C . Spectral studies on the calcium binding properties of bovine brain S-100b protein. Biochemistry. 1983; 22(7):1734-40. DOI: 10.1021/bi00276a033. View

13.

Gariepy J, Sykes B, Hodges R . Lanthanide-induced peptide folding: variations in lanthanide affinity and induced peptide conformation. Biochemistry. 1983; 22(8):1765-72. DOI: 10.1021/bi00277a004. View

14.

Satyshur K, Rao S, Pyzalska D, Drendel W, Greaser M, Sundaralingam M . Refined structure of chicken skeletal muscle troponin C in the two-calcium state at 2-A resolution. J Biol Chem. 1988; 263(4):1628-47. View

15.

Kretsinger R . Calcium coordination and the calmodulin fold: divergent versus convergent evolution. Cold Spring Harb Symp Quant Biol. 1987; 52:499-510. DOI: 10.1101/sqb.1987.052.01.057. View

16.

Herzberg O, James M . Refined crystal structure of troponin C from turkey skeletal muscle at 2.0 A resolution. J Mol Biol. 1988; 203(3):761-79. DOI: 10.1016/0022-2836(88)90208-2. View

17.

Babu Y, Bugg C, Cook W . Structure of calmodulin refined at 2.2 A resolution. J Mol Biol. 1988; 204(1):191-204. DOI: 10.1016/0022-2836(88)90608-0. View

18.

Sekharudu Y, Sundaralingam M . A structure-function relationship for the calcium affinities of regulatory proteins containing 'EF-hand' pairs. Protein Eng. 1988; 2(2):139-46. DOI: 10.1093/protein/2.2.139. View

19.

Strynadka N, James M . Crystal structures of the helix-loop-helix calcium-binding proteins. Annu Rev Biochem. 1989; 58:951-98. DOI: 10.1146/annurev.bi.58.070189.004511. View

20.

Swain A, Kretsinger R, Amma E . Restrained least squares refinement of native (calcium) and cadmium-substituted carp parvalbumin using X-ray crystallographic data at 1.6-A resolution. J Biol Chem. 1989; 264(28):16620-8. View