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. 1997 Dec;6(12):2494–2503. doi: 10.1002/pro.5560061202

Identification of the binding site on S100B protein for the actin capping protein CapZ.

P M Kilby 1, L J Van Eldik 1, G C Roberts 1
PMCID: PMC2143613  PMID: 9416599

Abstract

The calcium-binding protein S100B binds to several potential target proteins, but there is no detailed information showing the location of the binding site for any target protein on S100B. We have made backbone assignments of the calcium-bound form of S100B and used chemical-shift changes in spectra of 15N-labeled protein to locate the site that binds a peptide corresponding to residues 265-276 from CapZ alpha, the actin capping protein. The largest chemical-shift changes are observed for resonances arising from residues around the C terminus of the C-terminal helix of S100B and residues Val-8 to Asp-12 of the N-terminal helix. These residues are close to but not identical to residues that have been identified by mutational analysis to be important in other S100 protein-protein interactions. They make up a patch across the S100B dimer interface and include some residues that are quite buried in the structure of calcium-free S100B. We believe we may have identified a binding site that could be common to many S100 protein-protein interactions.

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Selected References

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  1. Baudier J., Delphin C., Grunwald D., Khochbin S., Lawrence J. J. Characterization of the tumor suppressor protein p53 as a protein kinase C substrate and a S100b-binding protein. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11627–11631. doi: 10.1073/pnas.89.23.11627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baudier J., Gérard D. Ions binding to S100 proteins: structural changes induced by calcium and zinc on S100a and S100b proteins. Biochemistry. 1983 Jul 5;22(14):3360–3369. doi: 10.1021/bi00283a009. [DOI] [PubMed] [Google Scholar]
  3. Bianchi R., Garbuglia M., Verzini M., Giambanco I., Ivanenkov V. V., Dimlich R. V., Jamieson G. A., Jr, Donato R. S-100 (alpha and beta) binding peptide (TRTK-12) blocks S-100/GFAP interaction: identification of a putative S-100 target epitope within the head domain of GFAP. Biochim Biophys Acta. 1996 Oct 11;1313(3):258–267. doi: 10.1016/0167-4889(96)00098-5. [DOI] [PubMed] [Google Scholar]
  4. Drohat A. C., Amburgey J. C., Abildgaard F., Starich M. R., Baldisseri D., Weber D. J. Solution structure of rat apo-S100B(beta beta) as determined by NMR spectroscopy. Biochemistry. 1996 Sep 10;35(36):11577–11588. doi: 10.1021/bi9612226. [DOI] [PubMed] [Google Scholar]
  5. Fujii T., Machino K., Andoh H., Satoh T., Kondo Y. Calcium-dependent control of caldesmon-actin interaction by S100 protein. J Biochem. 1990 Jan;107(1):133–137. doi: 10.1093/oxfordjournals.jbchem.a122996. [DOI] [PubMed] [Google Scholar]
  6. Fujii T., Oomatsuzawa A., Kuzumaki N., Kondo Y. Calcium-dependent regulation of smooth muscle calponin by S100. J Biochem. 1994 Jul;116(1):121–127. doi: 10.1093/oxfordjournals.jbchem.a124484. [DOI] [PubMed] [Google Scholar]
  7. Grzesiek S., Stahl S. J., Wingfield P. T., Bax A. The CD4 determinant for downregulation by HIV-1 Nef directly binds to Nef. Mapping of the Nef binding surface by NMR. Biochemistry. 1996 Aug 13;35(32):10256–10261. doi: 10.1021/bi9611164. [DOI] [PubMed] [Google Scholar]
  8. Haimoto H., Kato K. S100a0 (alpha alpha) protein in cardiac muscle. Isolation from human cardiac muscle and ultrastructural localization. Eur J Biochem. 1988 Jan 15;171(1-2):409–415. doi: 10.1111/j.1432-1033.1988.tb13805.x. [DOI] [PubMed] [Google Scholar]
  9. Heierhorst J., Kobe B., Feil S. C., Parker M. W., Benian G. M., Weiss K. R., Kemp B. E. Ca2+/S100 regulation of giant protein kinases. Nature. 1996 Apr 18;380(6575):636–639. doi: 10.1038/380636a0. [DOI] [PubMed] [Google Scholar]
  10. Hensmann M., Booker G. W., Panayotou G., Boyd J., Linacre J., Waterfield M., Campbell I. D. Phosphopeptide binding to the N-terminal SH2 domain of the p85 alpha subunit of PI 3'-kinase: a heteronuclear NMR study. Protein Sci. 1994 Jul;3(7):1020–1030. doi: 10.1002/pro.5560030704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ivanenkov V. V., Jamieson G. A., Jr, Gruenstein E., Dimlich R. V. Characterization of S-100b binding epitopes. Identification of a novel target, the actin capping protein, CapZ. J Biol Chem. 1995 Jun 16;270(24):14651–14658. doi: 10.1074/jbc.270.24.14651. [DOI] [PubMed] [Google Scholar]
  12. Johnsson N., Marriott G., Weber K. p36, the major cytoplasmic substrate of src tyrosine protein kinase, binds to its p11 regulatory subunit via a short amino-terminal amphiphatic helix. EMBO J. 1988 Aug;7(8):2435–2442. doi: 10.1002/j.1460-2075.1988.tb03089.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kilby P. M., Van Eldik L. J., Roberts G. C. Nuclear magnetic resonance assignments and secondary structure of bovine S100 beta protein. FEBS Lett. 1995 Apr 17;363(1-2):90–96. doi: 10.1016/0014-5793(95)00296-l. [DOI] [PubMed] [Google Scholar]
  14. Kilby P. M., Van Eldik L. J., Roberts G. C. The solution structure of the bovine S100B protein dimer in the calcium-free state. Structure. 1996 Sep 15;4(9):1041–1052. doi: 10.1016/s0969-2126(96)00111-6. [DOI] [PubMed] [Google Scholar]
  15. Kube E., Becker T., Weber K., Gerke V. Protein-protein interaction studied by site-directed mutagenesis. Characterization of the annexin II-binding site on p11, a member of the S100 protein family. J Biol Chem. 1992 Jul 15;267(20):14175–14182. [PubMed] [Google Scholar]
  16. Kördel J., Forsén S., Drakenberg T., Chazin W. J. The rate and structural consequences of proline cis-trans isomerization in calbindin D9k: NMR studies of the minor (cis-Pro43) isoform and the Pro43Gly mutant. Biochemistry. 1990 May 8;29(18):4400–4409. doi: 10.1021/bi00470a020. [DOI] [PubMed] [Google Scholar]
  17. Lackmann M., Rajasekariah P., Iismaa S. E., Jones G., Cornish C. J., Hu S., Simpson R. J., Moritz R. L., Geczy C. L. Identification of a chemotactic domain of the pro-inflammatory S100 protein CP-10. J Immunol. 1993 Apr 1;150(7):2981–2991. [PubMed] [Google Scholar]
  18. Lin L. H., Van Eldik L. J., Osheroff N., Norden J. J. Inhibition of protein kinase C- and casein kinase II-mediated phosphorylation of GAP-43 by S100 beta. Brain Res Mol Brain Res. 1994 Sep;25(3-4):297–304. doi: 10.1016/0169-328x(94)90165-1. [DOI] [PubMed] [Google Scholar]
  19. McAlister M. S., Mott H. R., van der Merwe P. A., Campbell I. D., Davis S. J., Driscoll P. C. NMR analysis of interacting soluble forms of the cell-cell recognition molecules CD2 and CD48. Biochemistry. 1996 May 14;35(19):5982–5991. doi: 10.1021/bi952756u. [DOI] [PubMed] [Google Scholar]
  20. Okazaki K., Obata N. H., Inoue S., Hidaka H. S100 beta is a target protein of neurocalcin delta, an abundant isoform in glial cells. Biochem J. 1995 Mar 1;306(Pt 2):551–555. doi: 10.1042/bj3060551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schäfer B. W., Heizmann C. W. The S100 family of EF-hand calcium-binding proteins: functions and pathology. Trends Biochem Sci. 1996 Apr;21(4):134–140. doi: 10.1016/s0968-0004(96)80167-8. [DOI] [PubMed] [Google Scholar]
  22. Sheu F. S., Azmitia E. C., Marshak D. R., Parker P. J., Routtenberg A. Glial-derived S100b protein selectively inhibits recombinant beta protein kinase C (PKC) phosphorylation of neuron-specific protein F1/GAP43. Brain Res Mol Brain Res. 1994 Jan;21(1-2):62–66. doi: 10.1016/0169-328x(94)90378-6. [DOI] [PubMed] [Google Scholar]
  23. Skelton N. J., Akke M., Kördel J., Thulin E., Forsén S., Chazin W. J. 15N NMR assignments and chemical shift analysis of uniformly labeled 15N calbindin D9k in the apo, (Cd2+)1 and (Ca2+)2 states. FEBS Lett. 1992 Jun 1;303(2-3):136–140. doi: 10.1016/0014-5793(92)80505-b. [DOI] [PubMed] [Google Scholar]
  24. Skelton N. J., Forsén S., Chazin W. J. 1H NMR resonance assignments, secondary structure, and global fold of Apo bovine calbindin D9k. Biochemistry. 1990 Jun 19;29(24):5752–5761. doi: 10.1021/bi00476a016. [DOI] [PubMed] [Google Scholar]
  25. Skelton N. J., Kördel J., Chazin W. J. Determination of the solution structure of Apo calbindin D9k by NMR spectroscopy. J Mol Biol. 1995 Jun 2;249(2):441–462. doi: 10.1006/jmbi.1995.0308. [DOI] [PubMed] [Google Scholar]
  26. Watanabe M., Ando Y., Tokumitsu H., Hidaka H. Binding site of annexin XI on the calcyclin molecule. Biochem Biophys Res Commun. 1993 Nov 15;196(3):1376–1382. doi: 10.1006/bbrc.1993.2405. [DOI] [PubMed] [Google Scholar]
  27. Wishart D. S., Sykes B. D., Richards F. M. The chemical shift index: a fast and simple method for the assignment of protein secondary structure through NMR spectroscopy. Biochemistry. 1992 Feb 18;31(6):1647–1651. doi: 10.1021/bi00121a010. [DOI] [PubMed] [Google Scholar]
  28. Zimmer D. B., Cornwall E. H., Landar A., Song W. The S100 protein family: history, function, and expression. Brain Res Bull. 1995;37(4):417–429. doi: 10.1016/0361-9230(95)00040-2. [DOI] [PubMed] [Google Scholar]
  29. Zimmer D. B., Dubuisson J. G. Identification of an S100 target protein: glycogen phosphorylase. Cell Calcium. 1993 Apr;14(4):323–332. doi: 10.1016/0143-4160(93)90053-9. [DOI] [PubMed] [Google Scholar]
  30. Zimmer D. B., Van Eldik L. J. Identification of a molecular target for the calcium-modulated protein S100. Fructose-1,6-bisphosphate aldolase. J Biol Chem. 1986 Aug 25;261(24):11424–11428. [PubMed] [Google Scholar]

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