Molecular Structure and Function of Crystallins

眼睛的组织依赖于密切调控的发育途径和专门的蛋白质家族。这些包括透镜的晶体蛋白。我们已经证明，在人类和其他物种中，晶体蛋白是通过一个称为基因招募的过程产生的。许多类晶体蛋白的起源和功能已被阐明。GS-晶体蛋白是成人透镜中主要的BG-晶体蛋白。gS基因的切除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是异常的，和蛋白质复合物？结晶？在细胞膜上。这表明在正常的透镜发育中，gS在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，其基因结构结合了B-和g-基因家族的特征，并且在小鼠的透镜、光感受器和RPE中表达。gN基因和cDNA已在几个物种中鉴定，该家族似乎是bg超家族进化的中间产物。EST分析的特点是在几个物种，特别是斑马鱼的晶体蛋白的完整的家庭。这揭示了gS、gN和gM家族的保守成员和α-晶体蛋白家族的新的第三成员。结构功能研究正在进行中。 g-晶体蛋白通常与白内障相关。我们发现小鼠的3号白内障是由内源性逆转录病毒插入到gE-晶状体蛋白基因中，产生异常蛋白质引起的。它还指出了小鼠基因组中活性ERV的来源

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