Macario Alberto J L, Malz Mona, Conway de Macario Everly
Wadsworth Center, New York State Department of Health, Division of Molecular Medicine; The University at Albany (SUNY), Albany, New York 12201-0509, USA.
Front Biosci. 2004 May 1;9:1318-32. doi: 10.2741/1328.
Newly made proteins must achieve a functional shape, the native configuration, before they can play their physiological roles in the cell. Proteins must also travel to the locale (e.g., the mitochondrion) in the cell where their functions are required. In these processes of folding into the native configuration and translocation to the place of work, proteins may be assisted by molecules called molecular chaperones. Stressors can unfold (denature) proteins, and genetic defects can cause misfolding and, in addition, both abnormalities can lead to polypeptide aggregation. Chaperones play a role in assisting refolding of partially denatured or misfolded proteins, thus preventing aggregation. Clearly, molecular chaperones are key cell components under normal, physiological circumstances, as well as in potentially harmful situations resulting from environmental or inherited factors. Hence, molecular chaperones constitute attractive targets for a variety of efforts aiming at improving the cell's performance, particularly under stress, to prevent disease, or at least to slow down its progression and to contain the deleterious effects of stress. In our efforts in this direction, we have undertaken to investigate the chaperoning systems of cells belonging to the phylogenetic domain Archaea. The findings reported here pertain to the distribution of the molecular chaperone machine, the chaperonins, and the prefoldins, among archaea. The genes hsp70(dnaK), hsp40(dnaJ), and grpE encoding the components of the molecular chaperone machine were present only in some archeaeal species: this contrasts with bacteria and eucarya, which do have the genes with no known exception. The group I, or bacterial, chaperonin-genes groEL and groES occured in the genomes of Methanosarcina species but were not found in any of the other archaea whose genomes have been sequenced. While all the archaea studied had between one and three chaperonins of group II (thermosome subunits), Methanosarcina acetivorans was exceptional since it had five of these chaperonins. This is the largest number of group II chaperonins ever found in a prokaryote. Furthermore, two of the M. acetivorans chaperonins were different from, albeit related to, the other known archaeal and eucaryal chaperonins of group II. Prefoldins were found in all archaea examined. Overall, the results provide clues to the evolution of the chaperoning systems, which must have played a critical role in survival since life started. Also, the data suggest new avenues of research for elucidating the evolution of assisted protein folding and for uncovering roles and interactions not yet described for these molecules.
新合成的蛋白质在能够在细胞中发挥其生理作用之前，必须形成功能性的形状，即天然构象。蛋白质还必须转运到细胞中需要其发挥功能的区域（如线粒体）。在折叠成天然构象以及转运到工作场所的这些过程中，蛋白质可能会得到一类称为分子伴侣的分子的协助。应激源可使蛋白质展开（变性），遗传缺陷可导致错误折叠，此外，这两种异常情况都可导致多肽聚集。伴侣蛋白在协助部分变性或错误折叠的蛋白质重新折叠方面发挥作用，从而防止聚集。显然，分子伴侣在正常生理情况下以及在由环境或遗传因素导致的潜在有害情况下都是关键的细胞成分。因此，分子伴侣成为各种旨在改善细胞性能（尤其是在应激状态下）、预防疾病或至少减缓疾病进展并控制应激有害影响的努力的有吸引力的靶点。在我们朝这个方向所做的努力中，我们着手研究属于古菌进化域的细胞的伴侣系统。此处报告的发现涉及分子伴侣机器、伴侣蛋白和前折叠蛋白在古菌中的分布。编码分子伴侣机器成分的基因hsp70（dnaK）、hsp40（dnaJ）和grpE仅存在于一些古菌物种中：这与细菌和真核生物形成对比，细菌和真核生物无一例外都拥有这些基因。第一类，即细菌型伴侣蛋白基因groEL和groES存在于甲烷八叠球菌属物种的基因组中，但在任何其他已测序基因组的古菌中均未发现。虽然所有研究的古菌都有1至3个第二类伴侣蛋白（热体亚基），但嗜乙酸甲烷八叠球菌却是例外，因为它有5个这类伴侣蛋白。这是在原核生物中发现的第二类伴侣蛋白的最大数量。此外，嗜乙酸甲烷八叠球菌的两个伴侣蛋白虽然与其他已知的古菌和真核生物的第二类伴侣蛋白相关，但却有所不同。在所检测的所有古菌中都发现了前折叠蛋白。总体而言，这些结果为伴侣系统的进化提供了线索，自生命起源以来，伴侣系统必定在生存中发挥了关键作用。此外，这些数据还为阐明辅助蛋白质折叠的进化以及揭示这些分子尚未描述的作用和相互作用提示了新的研究途径。
