Modeling the structural consequences of BEST1 missense mutations

Karina E. Guziewicz, Gustavo D. Aguirre, Barbara Zangerl

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Mutations in the bestrophin-1 gene (BEST1) are an important cause of inherited retinal disorders. Hitherto, over 100 unique allelic variants have been linked to the human BEST1 (hBEST1), and associated with disease phenotypes, broadly termed as bestrophinopathies. A spontaneous animal model recapitulating BEST1-related phenotypes, canine multifocal retinopathy (cmr), is caused by mutations in the canine gene ortholog (cBEST1). We have recently characterized molecular consequences of cmr, demonstrating defective protein trafficking as a result of G 161D (cmr2) mutation. To further investigate the pathological effects of BEST1 missense mutations, canine and human peptide fragments derived from the protein sequence have been studied in silico as models for early events in the protein folding. The results showed that G 161D as well as I 201T substitutions cause severe conformational changes in the structure of bestrophin-1, suggesting protein misfolding as an underlying disease mechanism. The comparative modeling studies expand our insights into BEST1 pathogenesis.
Original languageEnglish
Article number8
Pages (from-to)611-618
Number of pages8
JournalAdvances in Experimental Medicine and Biology
Publication statusPublished - 2012
Externally publishedYes


  • Best Vitelliform Macular Dystrophy
  • BEST1
  • Bestrophin-1
  • Canine Multifocal Retinopathy
  • Missense Mutations


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