Primary sequence contribution to the optical function of the eye lens

Abstract

The crystallins have relatively high refractive increments compared to other proteins. The Greek key motif in βγ-crystallins was compared with that in other proteins, using predictive analysis from a protein database, to see whether this may be related to the refractive increment. Crystallins with Greek keys motifs have significantly higher refractive increments and more salt bridges than other proteins with Greek key domains. Specific amino acid substitutions: lysine and glutamic acid residues are replaced by arginine and aspartic acid, respectively as refractive increment increases. These trends are also seen in S-crystallins suggesting that the primary sequence of crystallins may be specifically enriched with amino acids with appropriate values of refractive increment to meet optical requirements. Comparison of crystallins from five species: two aquatic and three terrestrial shows that the lysine/arginine correlation with refractive increment occurs in all species investigated. This may be linked with formation and maintenance of salt bridges.

Gamma crystallins of the human eye lens

“…It is noted that the dn/dc values of double Greek key domains are consistently higher (0.2009 ml/g for the Greek key motifs of crystallins, cf. 0.1899 for other human proteins [19]). Likewise, Zhao et al [20] had earlier argued that "one could speculate that this flexibility of the Greek key motif to accommodate different residues lends itself well as a stable scaffold for lens proteins, providing the opportunity of replacing residues with low dn/dc with high ones".…”

“…As Chen et al [12] point out, this template structure is highly conserved, thanks to several key residues in the sequence which play essential roles in the folding pattern, yet tolerates some variations in the non-essential residues in the sequence. The relation between the role of the Greek key structure and the values and gradients in the refractive index of lens proteins has been drawn attention to in some recent papers [19,20].…”

Biophysical chemistry of the ageing eye lens

“…Lens crystallins show high refractive index increments compared to other proteins, due to large quantities of aromatic and sulphurous residues (Mahendiran et al 2014), and show strong absorbance of UV radiation (Chen et al 2009;Zhao et al 2011). In humans, the fibre cells exhibit a protein concentration of ∼320 mg ml −1 uniformly throughout the lens (Bloemendal et al 2004).…”

“…They have a major role in generating the lens's high transparency and high refractive index (Mahendiran et al 2014;. This protein family is believed to have originated from primordial Archaeabacteria as single-domain Ca 2+ binding proteins (Barnwal et al 2009;Mishra et al 2014).…”

“…The βγ-crystallins are primarily responsible for the refractive index of the lens and tend to have an above average number of residues with high refractive index increments, i.e. aromatic (tyrosine, tryptophan and phenylalanine) and sulfur-containing (cysteine and methionine) amino acids (Mahendiran et al 2014;Zhao et al 2011). The highly soluble, highly stable, poly-dispersed nature of these proteins also minimises aggregation and crystallisation in the lens, ensuring high transparency (Piatigorsky et al 1994;Slingsby et al 2013).…”