Ameloblastin (AMBN) was originally believed to be an enamel-specific extracellular matrix glycoprotein secreted by ameloblasts. Recently, AMBN expression was also detected in developing mesenchymal dental hard tissues, in trauma-induced reparative dentin, and during early craniofacial bone formation. The function and structure of AMBN still remain ambiguous, and there are no known proteins with similar primary sequences. We therefore performed a bio-informatic analysis of AMBN to model ab initio the three-dimensional structure of the molecule. The results suggest that AMBN is a two-domain, intrinsically unstructured protein (IUP). The analysis did not reveal any regions with structural similarity to known receptor-ligand systems, and did not identify any higher-order structures similar to functional regions in other known sequences. The AMBN model predicts 11 defined regions exposed on the surface, internalizing the rest of the molecule including a human-specific insert. Molecular dynamics analysis identified one specific and several non-specific calcium-binding regions, mostly at the C-terminal part of the molecule. The model is supported by previous observations that AMBN is a bipolar calcium-binding molecule and hints at a possible role in protein-protein interactions. The model provides information useful for further studies on the function of AMBN.

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Flemingovo nam Prague Czech Republic

Citace poskytuje Crossref.org

Characterization of AMBN I and II Isoforms and Study of Their Ca2+-Binding Properties

An ameloblastin C-terminus variant is present in human adipose tissue

Phosphorylation Modulates Ameloblastin Self-assembly and Ca 2+ Binding

Mammalian enamel maturation: Crystallographic changes prior to tooth eruption

Ameloblastin Peptides Modulates the Osteogenic Capacity of Human Mesenchymal Stem Cells

Intrinsically disordered enamel matrix protein ameloblastin forms ribbon-like supramolecular structures via an N-terminal segment encoded by exon 5