Journal Article

PreJuSER-13705

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Fetuin-A is a mineral carrier protein: Small angle neutron scattering provides new insight on Fetuin-A controlled calcification inhibition

Heiss, A. ; Pipich, V.FZJ* ; Jahnen-Dechent, W. ; Schwahn, D.FZJ*

2010
Rockefeller Univ. Press New York, NY

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Please use a persistent id in citations: doi:10.1016/j.bpj.2010.10.030

Abstract: 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.

Keyword(s): Animals (MeSH) ; Calcification, Physiologic (MeSH) ; Calcium: metabolism (MeSH) ; Calcium Phosphates: metabolism (MeSH) ; Carrier Proteins: metabolism (MeSH) ; Cattle (MeSH) ; Colloids (MeSH) ; Minerals: metabolism (MeSH) ; Neutron Diffraction (MeSH) ; Protein Binding (MeSH) ; Scattering, Small Angle (MeSH) ; Time Factors (MeSH) ; Ultrafiltration (MeSH) ; alpha-Fetoproteins: metabolism (MeSH) ; Calcium Phosphates ; Carrier Proteins ; Colloids ; Minerals ; alpha-Fetoproteins ; Calcium ; J

Note: 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.

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Contributing Institute(s):

1. Neutronenstreuung (IFF-5)
2. Streumethoden (IFF-4)
3. JCNS (Jülich Centre for Neutron Science JCNS (JCNS) ; JCNS)

Research Program(s):

1. Großgeräte für die Forschung mit Photonen, Neutronen und Ionen (PNI) (P55)
2. BioSoft: Makromolekulare Systeme und biologische Informationsverarbeitung (P45)

Experiment(s):

1. KWS-2: Small angle scattering diffractometer (NL3ao)

Appears in the scientific report 2010

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