Disease relevance of BFSP2

• By sequencing the coding regions of BFSP2, we found that a deletion mutation, DeltaE233, is associated with cataracts in this family [1].
• A mutant strain of the cyanobacterium Synechocystis 6803, TolE4B, was constructed by genetic deletion of the protein that links phycobilisomes to thylakoid membranes and of the CP43 and CP47 proteins of photosystem II (PSII), leaving the photosystem I (PSI) center as the sole chromophore in the photosynthetic membranes [2].
• The intrinsic chlorophyll-protein CP 47 is a component of photosystem II in higher plants, green algae and cyanobacteria [3].

High impact information on BFSP2

• The recent publication of the sequences for two major lens filament proteins (CP49 and filensin) and the reconstitution in vitro of structures closely resembling beaded filaments, suggests that the beaded filament is related structurally to intermediate filaments (IFs) [4].
• BFs consist of filensin and phakinin, two recently characterized intermediate filament (IF) proteins [5].
• Filensin and phakinin copolymerize and form filamentous structures when expressed transiently in cultured cells [5].
• Quantitative immunoblotting with whole lens fiber cell preparations and fractions of washed lens membranes suggest that the natural stoichiometry of phakinin to filensin is approximately 3:1 [6].
• Modeling using the x-ray structure of cyanobacterial PSII suggests that energy transfer to the PSII reaction center is via the Chls bound to the CP47 and CP43 proteins [7].

Biological context of BFSP2

• Elsewhere, in family ADCC-3, we mapped an autosomal-dominant cataract gene to chromosome 3q21-q22, near the gene that encodes a lens-specific beaded filament protein gene, BFSP2 [1].
• 3) CP49 shows substitutions at 3 of 4 residues in the otherwise highly conserved intermediate filament protein motif LNDR [8].
• Amplification of CP 115 or CP 47 sequences in each of the somatic cell hybrid samples was correlated with the presence/absence of human genomic DNA sequences encoding the respective gene sequences [9].
• Further mapping using somatic cell lines carrying derivatives of human chromosome 3 localize the gene for CP 47 to 3q21-25 [9].
• A juvenile-onset, progressive cataract locus on chromosome 3q21-q22 is associated with a missense mutation in the beaded filament structural protein-2 [10].

Anatomical context of BFSP2

• On consideration of the proposed function of BFSP2 in the lens cytoskeleton, it is likely that this alteration is the cause of cataracts in the members of the family we studied [10].
• These data show that CP49 is a member of the intermediate filament family, but highly unusual in several regards [8].
• With immunoconfocal microscopy, regions of colocalization of AQP0 with filensin and CP49 at the fiber cell plasma membrane in the lens cortex were defined [11].
• It is proposed that both filensin and CP49 are critically involved in organising the cytoplasmic and plasma membrane domains of the fibre cell and therefore essential to the optical properties of the lens [12].
• Vitreous humor, the presumptive source of differentiation-promoting activity in vivo, contains a factor capable of diffusing out of the vitreous body and inducing delta-crystallin and CP49 expression in chick lens cultures [13].

Associations of BFSP2 with chemical compounds

• Sequencing results revealed a 3-bp deletion of nucleotides 696-698 (GAA) in exon 3 of BFSP2, which is predicted to cause an in-frame deletion of glutamic acid residue 233 from the polypeptide encoded by the mutant gene [14].
• Photoassembly of the manganese cluster and oxygen evolution from monomeric and dimeric CP47 reaction center photosystem II complexes [15].
• After the lower Ca(2+) affinity and the 10-fold smaller absorption cross-section for photons in CP47 dimers is taken into account, the intrinsic rate constant for the rate-limiting calcium-dependent dark step is indistinguishable for the two systems [15].
• Labeling of CP47, D2, and D1 with methylamine and phenylhydrazine approached a one-to-one stoichiometry, assuming that D2 and D1 each have one binding site [16].
• We have found, by using sucrose density centrifugation, that the resulting preparation consisted of a mixture of dimeric and monomeric forms of the CP47 reaction center (RC) complex, having molecular masses of 410 +/- 30 and 200 +/- 28 kDa, respectively, as estimated by size exclusion chromatography [17].

Other interactions of BFSP2

• The results obtained with MBP-alphaB were confirmed by immunoprecipitation reactions in which immunoprecipitation of native bovine alphaB-crystallin from heat-shocked lens cell homogenates resulted in the coprecipitation of phakinin and filensin [18].
• In addition, these results demonstrate a myopia susceptibility locus in this region, which might also be associated with the mutation in BFSP2 [19].

Analytical, diagnostic and therapeutic context of BFSP2

• Sequence analysis of the beaded filament structural protein 2 (BFSP2) gene identified a previously described c.697_699delGAA (E233del) mutation which was present in all individuals with Y-sutural cataract but not in unaffected individuals and controls [19].
• We have used the polymerase chain reaction (PCR) to amplify CP 115 and CP 47 encoding sequences from human lens cDNA samples [9].
• In addition, both low and high resolution radiation hybrid mapping of the CP49 gene has been completed, placing it very close to microsatellite marker D3S1290 on human chromosome 3q [20].
• Colocalization of AQP0 with filensin and CP49, two proteins identified after mass spectrometric analysis, were examined by immunoconfocal and immunoelectron microscopy of lens sections [11].
• The CP49 protein was undetectable by Western blot analysis [21].

References