Abstract

The S100 proteins are a major subfamily of EF-hand calcium binding proteins that are distinguished by cell type-specific expression and an unusual prevalence in a variety of disease states. This proposal seeks to address the role of zinc in modulating the functional properties of S100 proteins and will also explore the structural basis for the interaction of S100 proteins to cellular targets. The zinc bound states of three S100 systems will be examined, each having potentially distinct zinc binding modes. The structure and dynamics of four S100-target complexes will be examined in detail. These include complexes with protein ligands and small molecules. These results will link the large amount of experimental data available on S100 proteins and will help reveal the biophysical basis for their biological activity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM062112-01
Application #
6046306
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Program Officer
Wehrle, Janna P
Project Start
2000-03-01
Project End
2004-02-29
Budget Start
2000-03-01
Budget End
2001-02-28
Support Year
1
Fiscal Year
2000
Total Cost
$220,647
Indirect Cost

  Institution

Name
Vanderbilt University Medical Center
Department
Biochemistry
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212

  Publications

Liu, Janet Z; Jellbauer, Stefan; Poe, Adam J et al. (2012) Zinc sequestration by the neutrophil protein calprotectin enhances Salmonella growth in the inflamed gut. Cell Host Microbe 11:227-39
Rai, Vivek; Touré, Fatouma; Chitayat, Seth et al. (2012) Lysophosphatidic acid targets vascular and oncogenic pathways via RAGE signaling. J Exp Med 209:2339-50
Kehl-Fie, Thomas E; Chitayat, Seth; Hood, M Indriati et al. (2011) Nutrient metal sequestration by calprotectin inhibits bacterial superoxide defense, enhancing neutrophil killing of Staphylococcus aureus. Cell Host Microbe 10:158-64
Chazin, Walter J (2011) Relating form and function of EF-hand calcium binding proteins. Acc Chem Res 44:171-9
Ghavami, Saeid; Eshragi, Mehdi; Ande, Sudharsana R et al. (2010) S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3. Cell Res 20:314-31
Koch, Michael; Chitayat, Seth; Dattilo, Brian M et al. (2010) Structural basis for ligand recognition and activation of RAGE. Structure 18:1342-52
Ghavami, Saeid; Chitayat, Seth; Hashemi, Mohammad et al. (2009) S100A8/A9: a Janus-faced molecule in cancer therapy and tumorgenesis. Eur J Pharmacol 625:73-83
Zaia, A A; Sappington, K J; Nisapakultorn, K et al. (2009) Subversion of antimicrobial calprotectin (S100A8/S100A9 complex) in the cytoplasm of TR146 epithelial cells after invasion by Listeria monocytogenes. Mucosal Immunol 2:43-53
Ghavami, Saeid; Kerkhoff, Claus; Chazin, Walter J et al. (2008) S100A8/9 induces cell death via a novel, RAGE-independent pathway that involves selective release of Smac/DIABLO and Omi/HtrA2. Biochim Biophys Acta 1783:297-311
Corbin, Brian D; Seeley, Erin H; Raab, Andrea et al. (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319:962-5

Showing the most recent 10 out of 27 publications