Molecular Structure and Function of Crystallins

眼睛组织依赖于密切调节的发育途径和特殊蛋白质家族。这些包括晶状体的结晶蛋白。我们已经证明，在人类和其他物种中，晶体蛋白是通过一个叫做基因招募的过程产生的。许多类晶体蛋白的起源和功能已经被阐明。gs -晶状体蛋白是成人晶状体中主要的bg-晶状体蛋白。gS基因的消融导致正常纤维细胞组织和细胞核加工的破坏。特别是，肌动蛋白细胞骨架和细胞连接异常，蛋白质复合物结晶。在细胞膜中。这表明gS在正常晶状体发育的结构组织中起着关键的功能作用。我们发现了g-晶体蛋白家族的一个新成员gN，它的基因结构结合了b-和g-基因家族的特征，在小鼠的晶状体、光感受器和RPE中表达。gN基因和cdna已经在几个物种中被鉴定出来，这个家族似乎是bg超家族进化的中间产物。EST分析已经在一些物种，特别是斑马鱼中发现了完整的晶体蛋白家族。这揭示了gS， gN和gM家族的保守成员以及α -晶体蛋白家族的第三个新成员。结构功能研究正在进行中。

Tissues of the eye depend on closely regulated developmental pathways and families of specialized proteins. These include the crystallins of the lens. We have shown that in humans and other species, crystallins have arisen by a process called Gene Recruitment. The origins and functions of many classes of crystallins have been elucidated. gS-crystallin is the major bg-crystallin in the adult human lens. Ablation of the gene for gS leads to disruption of normal fiber cell organization and processing of cell nuclei. In particular, the actin cytoskeleton and cell junctions are aberrant, and protein complexes ?crystallize? in the cell membrane. This suggests a key functional role for gS in structural organization in normal lens development. We have discovered a new member of the g-crystallin family, gN, which has a gene structure that combines features of both b- and g- gene families and is expressed in lens, photoreceptors and RPE in mouse. gN gene and cDNAs have been identified in several species and this family seems to be an intermediate in the evolution of the bg superfamily. EST analyses have characterized complete families of crystallins in several species, particularly zebrafish. This has revealed conserved members of gS, gN and gM families and a novel, third member of the alpha-crystallin family. Structure function studies are in progress. g-Crystallins are often associated with cataract. We have found that the No3 cataract in mice is caused by insertion of an endogenous retrovirus into the gene for gE-crystallin, giving rise to an aberrant protein. It also points to a source of active ERV in the mouse genome