In vitro effects of recombinant otoconin 90 upon calcite crystal growth. Significance of tertiary structure

Abstract

Otoconia are biomineral particles of microscopic size essential for perception of gravity and maintenance of balance. Millions of older Americans are affected in their mobility, quality of life and in their health by progressive demineralization of otoconia. Currently, no effective means to prevent or counteract this process are available. Because of prohibitive anatomical and biological constraints, otoconial research is lagging far behind other systems such as bone and teeth. We have overcome these obstacles by generating otoconial matrix proteins by recombinant techniques. In the present study, we evaluated the effects of recombinant Otoconin 90 (OC90), the principal soluble matrix protein upon calcite crystal growth patterns in vitro. Our findings highlight multiple effects, including facilitation of nucleation, and inhibition of crystal growth in a concentration-dependent manner. Moreover, OC90 induces morphologic changes characteristic of native otoconia. OC90 is considerably less acidic than the prototypical invertebrate CaCO3 –associated protein, but is nevertheless an effective modulator of calcite crystal growth. Based on homology modeling of the sPLA2-like domains of OC90, we propose that the lower density of acidic residues of the primary sequence is compensated by formation of major anionic surface clusters upon folding into tertiary conformation.

Visuo-vestibular contributions to anxiety and fear

“…The otolithic organs detect the direction of the constant linear acceleration due to gravity (Lysakowski and Goldberg, 2004). The linear acceleration sensitivity is due to the fact that the kinocilia and stereocilia of the otolith organ hair cells are embedded in an otoconial membrane that is covered with calcite crystals that grow in the presence of the primary otoconial matrix protein, otoconin 90 (Lu et al, 2010). The mass of the otoconia and membrane confers linear acceleration sensitivity to the hair cells (Wilson and Melvill Jones, 1979).…”

Structural Relationship between Calcite–Gelatine Composites and Biogenic (Human) Otoconia

“…[31] In calcite otoconia of mammals and birds, the major protein is a highly glycosylated glycoprotein named otoconin 90 (more than 90 % of the soluble organic matrix). [32,33] The principal insoluble scaffold protein otolin contributes to the extracellular matrix of the inner ear and is responsible for the growth and anchoring of otoconia. [30,34,35] This protein has also been identified and partially characterised in otoliths of fish (teleosts) and is called otolin-1.…”

Otoconia: Mimicking a calcite-based functional material of the human body. From basic research to medical aspects

“…13 and shows the destructive force of calcium carbonate during attachment at/in collagen. The major organic component in otoconia of mammals (and birds) is a highly glycosylated protein, named otonin 90, coming to more than 90% of the soluble organic matrix [40,41]. The principal insoluble scaffold protein, otolin-1, contributes to the extracellular matrix of the inner ear, and is assumed to be responsible for the growth and anchoring of otoconia [42][43][44].…”