Aragonite-associated biomineralization proteins are disordered and contain interactive motifs

Bioinformatics. 2012 Dec 15;28(24):3182-5. doi: 10.1093/bioinformatics/bts604. Epub 2012 Oct 11.


Motivation: The formation of aragonite mineral in the mollusk shell or pearl nacre requires the participation of a diverse set of proteins that form the mineralized extracellular matrix. Although self-assembly processes have been identified for several nacre proteins, these proteins do not contain known globular protein-protein binding domains. Thus, we hypothesize that other sequence features are responsible for nacre matrix protein-protein assembly processes and ultimately aragonite biosynthesis.

Results: Of 39 mollusk aragonite-associated protein sequences, 100% contain at least one region of intrinsic disorder or unfolding, with the highest percentages found in framework and pearl-associated proteins relative to the intracrystalline proteins. In some instances, these intrinsically disordered regions were identified as bind/fold sequences, and a limited number correlate with known biomineral-relevant sequences. Interestingly, 95% of the aragonite-associated protein sequences were found to contain at least one occurrence of amyloid-like or cross-β strand aggregation-prone supersecondary motifs, and this correlates with known aggregation and aragonite formation functions in three experimentally tested protein sequences. Collectively, our findings indicate that aragonite-associated proteins have evolved signature sequence traits of intrinsic disorder and aggregation-prone regions that are important for their role(s) in matrix assembly and mineralization.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Calcification, Physiologic
  • Calcium Carbonate / chemistry*
  • Calcium Carbonate / metabolism
  • Extracellular Matrix Proteins / chemistry*
  • Mollusca / chemistry*
  • Mollusca / metabolism
  • Nacre / chemistry
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Sequence Analysis, Protein


  • Extracellular Matrix Proteins
  • Nacre
  • Calcium Carbonate