The Structural and Chemical Role of Fetuin-A in Biomineralization

• Applicant: Dr. Wolf-Alexander Heiß
• Subject Area: Biochemistry
• Term: from 2005 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5455056

Our work is focused on the ¿2 HS-glycoprotein / fetuin-A that is probably the most important systemic inhibitor of calcification. Fetuin-A deficient mice on a calcification sensitive DBA/2 genetic background develop massive calcifications throughout the body. After having identified the protein surface area that mediates the attachment to basic calcium phosphate surfaces, we also observed that the inhibition of mineral formation is based on colloidal fetuin-A mineral aggregates. We studied those particles using scattering methods and TEM. Within the next two years we will: · study the transformation of early amorphous fetuin-A mineral aggregates (calciprotein particles, CPP) to crystalline mature CPPs · produce CPPs and variants thereof for in vivo studies · model the docking of fetuin-A to apatite surfaces · develop an assay for the assessment of calcification risk in blood and support the development of synthetic inhibitors

• DFG Programme: Priority Programmes
• Subproject of: SPP 1117: Principles of Biomineralization