Chakrabortee Sohini, Boschetti Chiara, Walton Laura J, Sarkar Sovan, Rubinsztein David C, Tunnacliffe Alan
Institute of Biotechnology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QT, United Kingdom.
Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18073-8. doi: 10.1073/pnas.0706964104. Epub 2007 Nov 2.
The ability of certain plants, invertebrates, and microorganisms to survive almost complete loss of water has long been recognized, but the molecular mechanisms of this phenomenon remain to be defined. One phylogenetically widespread adaptation is the presence of abundant, highly hydrophilic proteins in desiccation-tolerant organisms. The best characterized of these polypeptides are the late embryogenesis abundant (LEA) proteins, first described in plant seeds >20 years ago but recently identified in invertebrates and bacteria. The function of these largely unstructured proteins has been unclear, but we now show that a group 3 LEA protein from the desiccation-tolerant nematode Aphelenchus avenae is able to prevent aggregation of a wide range of other proteins both in vitro and in vivo. The presence of water is essential for maintenance of the structure of many proteins, and therefore desiccation stress induces unfolding and aggregation. The nematode LEA protein is able to abrogate desiccation-induced aggregation of the water-soluble proteomes from nematodes and mammalian cells and affords protection during both dehydration and rehydration. Furthermore, when coexpressed in a human cell line, the LEA protein reduces the propensity of polyglutamine and polyalanine expansion proteins associated with neurodegenerative diseases to form aggregates, demonstrating in vivo function of an LEA protein as an antiaggregant. Finally, human cells expressing LEA protein exhibit increased survival of dehydration imposed by osmotic upshift, consistent with a broad protein stabilization function of LEA proteins under conditions of water stress.
某些植物、无脊椎动物和微生物几乎在完全失水的情况下仍能存活，这一现象早已为人所知，但这种现象的分子机制仍有待确定。一种在系统发育上广泛存在的适应性特征是，耐旱生物中存在大量高度亲水的蛋白质。这些多肽中研究得最清楚的是胚胎后期丰富（LEA）蛋白，20多年前首次在植物种子中被描述，但最近在无脊椎动物和细菌中也被发现。这些大多无结构的蛋白质的功能一直不清楚，但我们现在表明，来自耐旱线虫燕麦真滑刃线虫的第3组LEA蛋白在体外和体内都能够防止多种其他蛋白质聚集。水的存在对于维持许多蛋白质的结构至关重要，因此脱水胁迫会导致蛋白质展开和聚集。线虫LEA蛋白能够消除脱水诱导的线虫和哺乳动物细胞水溶性蛋白质组的聚集，并在脱水和复水过程中提供保护。此外，当在人类细胞系中共表达时，LEA蛋白降低了与神经退行性疾病相关的聚谷氨酰胺和聚丙氨酸扩展蛋白形成聚集体的倾向，证明了LEA蛋白在体内作为抗聚集剂的功能。最后，表达LEA蛋白的人类细胞在渗透压升高引起的脱水过程中存活率增加，这与LEA蛋白在水分胁迫条件下具有广泛的蛋白质稳定功能一致。
