MOLECULAR BIOLOGY, STRUCTURES AND FUNCTION OF CRYSTALLINS

眼睛的组织依赖于专门的蛋白质家族。在透镜中，主要的蛋白质是晶体蛋白.我们已经证明，在人类和其他物种中，晶体蛋白是通过一种称为基因招募的过程产生的。蛋白质如酶和应激蛋白已被招募来在透镜透明度中起额外的结构作用。许多类晶体蛋白的起源和功能已被阐明。目前，我们正在研究最后一个功能未知的主要群体。这些是相关的β（B）和γ（g）晶体蛋白。这些蛋白质的非晶状体亲属与压力和癌症相关的功能已被确定。这包括一种在人类视网膜色素上皮细胞中表达的新基因。我们还发现gS晶体蛋白和bA 2晶体蛋白具有非晶状体表达，可能反映了非晶状体功能。这两种蛋白质的基因已经测序。我们已经表明，gS是位点的Opj白内障在小鼠中，并有证据表明，在控制纤维细胞结构的功能丧失。已经产生了gS的重组野生型和突变体蛋白用于功能研究。Opj中的突变蛋白含有温度敏感的不稳定突变。在小鼠体温附近，一个结构域展开并导致蛋白质变得不可溶。在某些物种中，酶被募集为晶体蛋白。我们已经生产了其中之一的重组蛋白，eta-晶状体蛋白，这是一种视黄醇脱氢酶。与伯克贝克学院小组合作确定了晶体结构。我们还表达了mu-crystallin，一种功能未知但可能参与异常氨基酸代谢的酶，这种酶也与某些人类疾病有关。

Tissues of the eye depend on families of specialized proteins. In the lens, the major proteins the crystallins. We have shown that in humans and other species, crystallins have arisen by a process called Gene Recruitement. Proteins such as enzymes and stress proteins have been recruited to serve an additionl structural role in lens transparency. The origins and functions of many classes of crystallins have been elucidated. Currently we are investigating the last major group for which a function is unknown. These are the related beta(b) and gamma (g) crystallins. Non-lens relatives of these proteins with stress and cancer related functions have been identified. This includes a novel gene expressed in human retinal pigment epithelium. We have also shown that gS crystallin and bA2 crystallin have non-lens expression possibly relecting a non-lens function. The genes for both these proteins have been sequenced. We have shown that gS is the locus of the Opj cataract in mouse and have evidence for loss of function in control of fiber cell structure. Recombinant wild type and mutant proteins for gS have been produced for functional studies. The mutant protein in Opj contains a temperature-sensitive destablizing mutation. Around mouse body temperature one domain unfolds and causes the protein to become insoluble. In some species enzymes have been recruited as crystallins. We have produced recombinant protein for one of these, eta-crystallin, which is a retinaldehyde dehydrogenase. A crystal structure has been determined in collaboration with the Birkbeck College group. We have also expressed mu-crystallin, an enzyme of unknown function but probably involved in unusual amino-acid metabolism which is also implicated in some human diseases.