Best1 Shot Through the Eye—Structure, Functions and Clinical Implications of Bestrophin-1 Protein

Moskova-Doumanova, Veselina; Pankov, Roumen; Lalchev, Zdravko; Doumanov, Jordan

doi:10.5504/bbeq.2012.0124

Cited by 6 publications

(3 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The N-terminus of this protein (amino acids 1–390) contains all of the putative membrane-spanning domains and is sufficient for its CaCC activity while the carboxy-terminal region (amino acids 391–585 of BEST1) is predicted to be unstructured 54 . Structural models of BEST1 have been proposed, which describe topological positions of the N-terminal region, the transmembrane domains and the C-terminus 55 , 56 . Such models propose the N- and C-termini as being cytosolic with the presence of four transmembrane domains (domain 1,2 and 5, 6) while domain 3 and 4 are cytoplasmic 55 , 56 (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Structural models of BEST1 have been proposed, which describe topological positions of the N-terminal region, the transmembrane domains and the C-terminus 55 , 56 . Such models propose the N- and C-termini as being cytosolic with the presence of four transmembrane domains (domain 1,2 and 5, 6) while domain 3 and 4 are cytoplasmic 55 , 56 (Fig. 7a–c ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Next generation sequencing identifies novel disease-associated BEST1 mutations in Bestrophinopathy patients

Nguyen¹,

Poornachandra

Verma

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Bestinopathies are a spectrum of retinal disorders associated with mutations in BEST1 including autosomal recessive bestrophinopathy (ARB) and autosomal dominant Best vitelliform macular dystrophy (BVMD). We applied whole-exome sequencing on four unrelated Indian families comprising eight affected and twelve unaffected individuals. We identified five mutations in BEST1, including p.Tyr131Cys in family A, p.Arg150Pro in family B, p.Arg47His and p.Val216Ile in family C and p.Thr91Ile in family D. Among these, p.Tyr131Cys, p.Arg150Pro and p.Val216Ile have not been previously reported. Further, the inheritance pattern of BEST1 mutations in the families confirmed the diagnosis of ARB in probands in families A, B and C, while the inheritance of heterozygous BEST1 mutation in family D (p.Thr91Ile) was suggestive of BVMD. Interestingly, the ARB families A and B carry homozygous mutations while family C was a compound heterozygote with a mutation in an alternate BEST1 transcript isoform, highlighting a role for alternate BEST1 transcripts in bestrophinopathy. In the BVMD family D, the heterozygous BEST1 mutation found in the proband was also found in the asymptomatic parent, suggesting an incomplete penetrance and/or the presence of additional genetic modifiers. Our report expands the list of pathogenic BEST1 genotypes and the associated clinical diagnosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Next generation sequencing identifies novel disease-associated BEST1 mutations in Bestrophinopathy patients

Nguyen¹,

Poornachandra

Verma

et al. 2018

Sci Rep

View full text Add to dashboard Cite

show abstract

“…BVMD is linked to mutations in the Bestrophin-1 gene ( BEST1 , formerly VMD2 ) located on chromosome 11 [5,6]. Mutations in BEST1 are associated with phenotypic heterogeneity and cause five clinically distinct human diseases—the classical BVMD, adult-onset vitelliform macular dystrophy (AVMD), autosomal dominant vitreoretinochoroidopathy (ADVIRC), autosomal recessive bestrophinopathy (ARB) [7] and retinitis pigmentosa (RP) [8–10]. The BEST1 gene encodes the 585-amino acid protein bestrophin-1 (Best1) with an expected molecular mass of 68 kDa.…”

Section: Introductionmentioning

confidence: 99%

Disease-Causing Mutations in BEST1 Gene Are Associated with Altered Sorting of Bestrophin-1 Protein

Doumanov

Zeitz

Gimenez

et al. 2013

IJMS

Self Cite

View full text Add to dashboard Cite

Mutations in BEST1 gene, encoding the bestrophin-1 (Best1) protein are associated with macular dystrophies. Best1 is predominantly expressed in the retinal pigment epithelium (RPE), and is inserted in its basolateral membrane. We investigated the cellular localization in polarized MDCKII cells of disease-associated Best1 mutant proteins to study specific sorting motifs of Best1. Real-time PCR and western blots for endogenous expression of BEST1 in MDCK cells were performed. Best1 mutant constructs were generated using site-directed mutagenesis and transfected in MDCK cells. For protein sorting, confocal microscopy studies, biotinylation assays and statistical methods for quantification of mislocalization were used. Analysis of endogenous expression of BEST1 in MDCK cells revealed the presence of BEST1 transcript but no protein. Confocal microscopy and quantitative analyses indicate that transfected normal human Best1 displays a basolateral localization in MDCK cells, while cell sorting of several Best1 mutants (Y85H, Q96R, L100R, Y227N, Y227E) was altered. In contrast to constitutively active Y227E, constitutively inactive Y227F Best1 mutant localized basolaterally similar to the normal Best1 protein. Our data suggest that at least three basolateral sorting motifs might be implicated in proper Best1 basolateral localization. In addition, non-phosphorylated tyrosine 227 could play a role for basolateral delivery.

show abstract

Interaction of Bestrophin-1 with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) in surface films

Mladenova

Petrova

Georgiev

et al. 2014

Colloids and Surfaces B: Biointerfaces

View full text Add to dashboard Cite

Best1 Shot Through the Eye—Structure, Functions and Clinical Implications of Bestrophin-1 Protein

Cited by 6 publications

References 57 publications

Next generation sequencing identifies novel disease-associated BEST1 mutations in Bestrophinopathy patients

Next generation sequencing identifies novel disease-associated BEST1 mutations in Bestrophinopathy patients

Disease-Causing Mutations in BEST1 Gene Are Associated with Altered Sorting of Bestrophin-1 Protein

Interaction of Bestrophin-1 with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) in surface films

Contact Info

Product

Resources

About