title: Significance of tertiary conformation of otoconial matrix proteins - clinical implications.
abstract: CONCLUSIONS
  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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Washington University in St Louis, Missouri, USA. Thalmannr@ent.wustl.edu
authors.forename: Ruediger
authors.initials: R
authors.lastname: Thalmann
authors.forename: Isolde
authors.initials: I
authors.lastname: Thalmann
authors.forename: Wenfu
authors.initials: W
authors.lastname: Lu
mesh_terms: D000375:Aging / Q000378:metabolism; D029845:Amphibian Proteins / Q000737:chemistry; D000818:Animals; D002119:Calcium Carbonate / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002460:Cell Line; D003460:Crystallization; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008958:Models, Molecular; D010037:Otolithic Membrane / Q000378:metabolism*; D054497:Phospholipases A2, Secretory / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011892:Rana catesbeiana; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D029845:Amphibian Proteins; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; C512837:Oc90 protein, mouse; D011994:Recombinant Proteins; D054497:Phospholipases A2, Secretory; D002119:Calcium Carbonate