TY  - JOUR
AU  - Heiss, A.
AU  - Pipich, V.
AU  - Jahnen-Dechent, W.
AU  - Schwahn, D.
TI  - Fetuin-A is a mineral carrier protein: Small angle neutron scattering provides new insight on Fetuin-A controlled calcification inhibition
JO  - Biophysical journal
VL  - 99
SN  - 0006-3495
CY  - New York, NY
PB  - Rockefeller Univ. Press
M1  - PreJuSER-13705
SP  - 3986 - 3995
PY  - 2010
N1  - This study was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft) within the priority program "Principles of Biomineralization. A. Heiss thanks Prof. J. Mayer (GFE, Rheinisch-Westfalische Technische Hochschule, Aachen University) for supporting the project.
AB  - Clinical studies and animal experiments have shown that the serum protein fetuin-A is a highly effective inhibitor of soft tissue calcification. This inhibition mechanism was elucidated on the basis of an in vitro fetuin-A-mineral model system. In a previous study, we found that in a two-stage process ∼100-nm sized calciprotein particles (CPPs) were formed whose final stage was stabilized by a compact outer fetuin-A monolayer against further growth. Quantitative small-angle neutron scattering data analysis revealed that even at a fetuin-A concentration close to the stability limit, only approximately one-half of the mineral ions and only 5% of the fetuin-A were contained in the CPPs. To uncover the interplay of the remaining supersaturated mineral ion fraction and of the 95% non-CPP fetuin-A, we explored the fetuin-A monomer fraction in solution by contrast variation small-angle neutron scattering. Our results suggest that the mineral ions coalesce to subnanometer-sized clusters, reminiscent of Posner clusters, which are stabilized by fetuin-A monomers. Hence, our experiments revealed a second mechanism of long-term mineral ion stabilization by the fetuin-A that is complementary to the formation of CPPs.
KW  - Animals
KW  - Calcification, Physiologic
KW  - Calcium: metabolism
KW  - Calcium Phosphates: metabolism
KW  - Carrier Proteins: metabolism
KW  - Cattle
KW  - Colloids
KW  - Minerals: metabolism
KW  - Neutron Diffraction
KW  - Protein Binding
KW  - Scattering, Small Angle
KW  - Time Factors
KW  - Ultrafiltration
KW  - alpha-Fetoproteins: metabolism
KW  - Calcium Phosphates (NLM Chemicals)
KW  - Carrier Proteins (NLM Chemicals)
KW  - Colloids (NLM Chemicals)
KW  - Minerals (NLM Chemicals)
KW  - alpha-Fetoproteins (NLM Chemicals)
KW  - Calcium (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:21156141
C2  - pmc:PMC3000477
UR  - <Go to ISI:>//WOS:000285438900022
DO  - DOI:10.1016/j.bpj.2010.10.030
UR  - https://juser.fz-juelich.de/record/13705
ER  -