Borrás T, Jörnvall H, Rodokanaki A, Gonzalez P, Rodriguez I, Hernandez-Calzadilla C
Laboratory of Mechanisms of Ocular Diseases, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
Exp Eye Res. 1990 Jun;50(6):729-35. doi: 10.1016/0014-4835(90)90122-b.
Zeta-Crystallin, a major component of the guinea-pig lens proteins, is distantly related to the enzymes of the zinc-containing alcohol dehydrogenase family (ADH). Analysis of the structural similarities between zeta-crystallin and ADH reveals that while characteristics important in maintaining the tertiary structure of the molecule appear conserved, the amino acids binding the catalytic zinc atom are absent in zeta-crystallin. Significantly, zeta-crystallin does not have ADH activity. Previous studies showed that the zeta-crystallin protein is modified in the lens of guinea-pigs affected with an autosomal dominant hereditary cataract. We have further investigated the molecular origin of the lens defect by examining the steady-state levels of zeta-crystallin transcripts in normal and mutant eyes. Our data indicate that no normal zeta-crystallin mRNA is present in the lens of the homozygous animals; instead, a cross-hybridizing lower molecular weight mRNA is detected at significantly reduced concentrations. Heterozygous lenses exhibit both mRNA species.
ζ-晶状体蛋白是豚鼠晶状体蛋白的主要成分，与含锌乙醇脱氢酶家族（ADH）的酶有较远的亲缘关系。对ζ-晶状体蛋白和ADH之间结构相似性的分析表明，虽然在维持分子三级结构中重要的特征似乎是保守的，但ζ-晶状体蛋白中不存在结合催化锌原子的氨基酸。值得注意的是，ζ-晶状体蛋白没有ADH活性。先前的研究表明，ζ-晶状体蛋白在患有常染色体显性遗传性白内障的豚鼠晶状体中发生了修饰。我们通过检测正常和突变眼中ζ-晶状体蛋白转录本的稳态水平，进一步研究了晶状体缺陷的分子起源。我们的数据表明，纯合动物的晶状体中不存在正常的ζ-晶状体蛋白mRNA；相反，检测到一种杂交的低分子量mRNA，其浓度显著降低。杂合晶状体同时显示这两种mRNA。
