Abstract

Fish otoliths, biominerals composed of calcium carbonate with a small amount of organic matrix, are involved in the functioning of the inner ear. Starmaker (Stm) from zebrafish (Danio rerio) was the first protein found to be capable of controlling the formation of otoliths. Recently, a gene was identified encoding the Starmaker-like (Stm-l) protein from medaka (Oryzias latipes), a putative homologue of Stm and human dentine sialophosphoprotein. Although there is no sequence similarity between Stm-l and Stm, Stm-l was suggested to be involved in the biomineralization of otoliths, as had been observed for Stm even before. The molecular properties and functioning of Stm-l as a putative regulatory protein in otolith formation have not been characterized yet. A comprehensive biochemical and biophysical analysis of recombinant Stm-l, along with in silico examinations, indicated that Stm-l exhibits properties of a coil-like intrinsically disordered protein. Stm-l possesses an elongated and pliable structure that is able to adopt a more ordered and rigid conformation under the influence of different factors. An in vitro assay of the biomineralization activity of Stm-l indicated that Stm-l affected the size, shape and number of calcium carbonate crystals. The functional significance of intrinsically disordered properties of Stm-l and the possible role of this protein in controlling the formation of calcium carbonate crystals is discussed.

Highlights

  • Otoliths in teleost fish and otoconia in mammals are involved in the function of the inner ear, the sensory organ that plays an important role in hearing and balance [1, 2]

  • Preliminary size-exclusion chromatography (SEC) experiments showed that Stm-l had an elution volume that corresponded to a protein with a higher apparent molecular mass

  • All biologically controlled calcium carbonate minerals are associated with an organic matrix, which is involved in essential functions such as crystal nucleation, the control of crystal shape, the inhibition of crystal growth and act as a template for depositing crystals [7]

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Summary

Introduction

Otoliths in teleost fish and otoconia in mammals are involved in the function of the inner ear, the sensory organ that plays an important role in hearing and balance [1, 2]. Several human disorders are associated with otoconia deficiency, dislocation, malformation, or age-related degeneration [3,4,5] Both otoliths and otoconia are composed of calcium carbonate with a small amount of organic matrix composed of a mixture of different macromolecular components, including proteins, saccharides, glycans, and lipids [6]. It has been shown that many organic matrix proteins are extremely acidic and have extensive post-translational modifications [8] They often belong to the family of intrinsically disordered proteins (IDPs) [9], a class of proteins devoid of a rigid tertiary structure [10,11,12]

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