The molecular refractive function of lens γ-Crystallins.

The molecular refractive function of lens γ-Crystallins.
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DOI:
10.1016/j.jmb.2011.06.007
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发表时间:
2011-08-19
影响因子:
5.6
通讯作者:
Schuck P
Schuck P
中科院分区:
生物学2区
文献类型:
--
作者:
Zhao H;Brown PH;Magone MT;Schuck P

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γ-晶状体蛋白构成脊椎动物眼透镜核中的主要蛋白质组分。在非常高的浓度下,它们表现出极高的溶解度和热力学稳定性,以防止光散射和白内障的形成。然而,这一结构性作用之外的职能大多仍不清楚。在这里,我们计算晶体蛋白的分子折射率增量。我们发现所有的透镜γ-晶体蛋白都进化出了显著升高的分子折射率增量,这远高于大多数蛋白质,包括来自不同物种的βγ-晶体蛋白家族的非透镜成员。相同的特征在不同门的晶体蛋白中平行进化,包括头足类的S-晶体蛋白。高折射率增量可以降低实现透镜的合适屈光力所需的晶状体蛋白浓度,从而降低它们聚集和形成白内障的倾向。为了产生折射率增量的显著增加,需要氨基酸组成的实质性整体移位,这可以自然地解释γ-晶体蛋白及其功能同系物的高度不寻常的氨基酸组成。这一功能为解释其分子结构提供了新的视角。
γ-crystallins constitute the major protein component in the nucleus of the vertebrate eye lens. Present at very high concentrations, they exhibit extreme solubility and thermodynamic stability to prevent scattering of light and the formation of cataracts. However, functions beyond this structural role have remained mostly unclear. Here, we calculate molecular refractive index increments of crystallins. We show that all lens γ-crystallins have evolved a significantly elevated molecular refractive index increment, which is far above those of most proteins, including non-lens members of the βγ-crystallin family from different species. The same trait has evolved in parallel in crystallins of different phyla, including in the S-crystallins of cephalopods. A high refractive index increment can lower the crystallin concentration required to achieve a suitable refractive power of the lens, and thereby reduce their propensity to aggregate and form cataract. To produce a significant increase of the refractive index increment, a substantial global shift in the amino acid composition is required, which can naturally explain the highly unusual amino acid composition of γ-crystallins and their functional homologues. This function provides a new perspective for interpreting their molecular structure.
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