MOLECULAR BIOLOGY, STRUCTURES AND FUNCTION OF CRYSTALLINS

眼睛的组织依赖于特化蛋白质家族。晶状体中的主要蛋白质是晶状体蛋白.我们已经证明，在人类和其他物种中，晶体蛋白是通过一种名为基因重复生成的过程产生的。酶和应激蛋白等蛋白质已经被招募来在晶状体透明度方面发挥额外的结构作用。许多种类的晶体蛋白的起源和功能已被阐明。目前，我们正在调查最后一个功能未知的主要群体。这些是相关的贝塔(B)和伽马(G)晶体蛋白。这些具有应激和癌症相关功能的蛋白质的非晶状体亲属已经被鉴定出来。这包括一种在人视网膜色素上皮中表达的新基因。我们还发现GS晶状体蛋白和Ba2晶状体蛋白有非晶状体表达，可能与非晶状体功能有关。这两种蛋白质的基因都已经测序。我们已经证明GS是小鼠OPJ白内障的基因位点，并且有证据表明GS失去了控制纤维细胞结构的功能。重组野生型和突变型GS蛋白已被用于功能研究。OPJ中的突变蛋白包含一个对温度敏感的不稳定突变。在老鼠的体温附近，一个结构域展开，导致蛋白质变得不能溶解。在某些物种中，酶被招募为晶状体蛋白。我们已经为其中之一生产了重组蛋白ETA-晶状体蛋白，它是一种视黄醛脱氢酶。已经与伯克贝克学院小组合作确定了一种晶体结构。我们还表达了结晶素，这是一种功能未知但可能参与异常氨基酸代谢的酶，也与一些人类疾病有关。

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.