ArticleThe Journal of biological chemistry2009
Human disease-causing mutations disrupt an N-C-terminal interaction and channel function of bestrophin 1.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Case Report: Acute angle-closure glaucoma as the initial presentation of autosomal recessive bestrophinopathy caused by compound heterozygousFrontiers in medicine · 2026Article
- Impaired Bestrophin Channel Activity in an iPSC-RPE Model of Best Vitelliform Macular Dystrophy (BVMD) from an Early Onset Patient Carrying the P77S Dominant Mutation.International journal of molecular sciences · 2022Article
- Genetic variations in Bestrophin‑1 and associated clinical findings in two Chinese patients with juvenile‑onset and adult‑onset best vitelliform macular dystrophy.Molecular medicine reports · 2018Article
- Multimodal imaging of adult-onset foveomacular vitelliform dystrophy.Saudi journal of ophthalmology : official journal of the Saudi Ophthalmological Society · 2014Article
- Effects of alternative splicing on the function of bestrophin-1 calcium-activated chloride channels.The Biochemical journal · 2014Article
- Differential effects of Best disease causing missense mutations on bestrophin-1 trafficking.Human molecular genetics · 2013Article
- Modeling the structural consequences of BEST1 missense mutations.Advances in experimental medicine and biology · 2012Article
- Molecular consequences of BEST1 gene mutations in canine multifocal retinopathy predict functional implications for human bestrophinopathies.Investigative ophthalmology & visual science · 2011Article
- Autosomal dominant Best disease with an unusual electrooculographic light rise and risk of angle-closure glaucoma: a clinical and molecular genetic study.Molecular vision · 2011Article
- Assessment of canine BEST1 variations identifies new mutations and establishes an independent bestrophinopathy model (cmr3).Molecular vision · 2010Article
- Phosphorylation and modulation of hyperpolarization-activated HCN4 channels by protein kinase A in the mouse sinoatrial node.The Journal of general physiology · 2010Article
- Bestrophins and retinopathies.Pflugers Archiv : European journal of physiology · 2010Review
- Chloride channels: often enigmatic, rarely predictable.Annual review of physiology · 2010Review
- Missense mutations in a retinal pigment epithelium protein, bestrophin-1, cause retinitis pigmentosa.American journal of human genetics · 2009Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Mutations in the human bestrophin 1 (hBest1) chloride channel cause Best vitelliform macular dystrophy. Although mutations in its transmembrane domains were found to alter biophysical properties of the channel, the mechanism for disease-causing mutations in its N and C termini remains elusive. We hypothesized that these mutations lead to channel dysfunction through disruption of an N-C-terminal interaction. Here, we present data demonstrating that hBest1 N and C termini indeed interact both in vivo and in vitro. In addition, using a spectrum-based fluorescence resonance energy transfer method, we showed that functional hBest1 channels in the plasma membrane were multimers. Disease-causing mutations in the N terminus (R19C, R25C, and K30C) and the C terminus (G299E, D301N, and D312N) caused channel dysfunction and disruption of the N-C interaction. Consistent with the functional and biochemical results, mutants D301N and D312N clearly reduced fluorescence resonance energy transfer signal, indicating that the N-C interaction was indeed perturbed. These results suggest that hBest1 functions as a multimer in the plasma membrane, and disruption of the N-C interaction by mutations leads to hBest1 channel dysfunction.
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