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ORIGINAL ARTICLE

Significance of tertiary conformation of otoconial matrix proteins – clinical implications

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Pages 382-390 | Received 20 Sep 2010, Accepted 28 Nov 2010, Published online: 14 Mar 2011
 

Abstract

Conclusion: Co-option of the enzyme secretory phospholipase A2 (sPLA2) and adoption of tertiary conformation are essential factors in the multifunctionality of otoconin 90 (OC90) and homologous modulators. Objective: To present results of in vitro studies of recombinant otoconial proteins for the understanding of current concepts of biomolecular mechanisms controlling otoconial mineralization. Methods: In vitro characterization of recombinant otoconial proteins with respect to crystal growth parameters and solution state behavior. Evaluation by HR-SEM, micro-Raman, circular dichroism, in combination with molecular modeling of individual domains and whole OC90. Results: Polymorph selection: recombinant otoconin 22 (rOC22) in vitro selects calcite rather than aragonite, expression of which requires association with an insoluble scaffold most likely provided by Otolin. Alternate folding of rOC22 results in formation of vaterite, the polymorph of primitive fish otoconia and of diseased human otoconia (e.g. Potter's syndrome). Molecular models of OC90 exhibit a surface of uniform negative electrostatic potential, enabling localized supersaturation. We propose that OC90 interacts with Otolin in formation of iso-oriented columns of nano-crystallites, which should ultimately result in assembly of the complex mosaic of native otoconia.

Acknowledgments

This study was supported by DC 009320 (RT) from the National Institute on Deafness and other Communication Disorders, NIH.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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