Molecular chaperones are nanomachines that catalytically unfold misfolded and alternatively folded proteins.
Molecular chaperones are nanomachines that catalytically unfold misfolded and alternatively folded proteins.
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DOI：
10.1007/s00018-014-1627-y
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发表时间：
2014-09
影响因子：
8
通讯作者：
Goloubinoff, Pierre
中科院分区：
文献类型：
--
作者：
Mattoo, Rayees U. H.;Goloubinoff, Pierre
由于分子伴侣具有结合(保持)、移位或展开原本注定要聚集的多肽的能力，因此通常被称为“保持酶”。然而，伴侣也具有不需要防止聚集的生理功能，如改变蛋白质的天然状态，如在拆解SNARE复合体和笼状蛋白外壳时。为了实现这些生理功能，Hsp70、Hsp110、Hsp100和Hsp60/CCT伴侣蛋白家族的主要成员作为催化去折叠酶或去折叠酶来驱动蛋白质结合、去折叠/拉动和释放的迭代循环。因此，一个去折叠酶伴侣可以连续地将许多错误折叠或交替折叠的多肽底物转化为瞬时展开的中间体，一旦释放，这些中间体可以自发地重新折叠成低亲和力的天然产物。然而，在胁迫期间，大量的非催化伴侣在保持模式下可能最好地阻止蛋白质聚集，在胁迫之后，催化解聚酶和解折叠酶可能充当纳米机器，利用ATP水解的能量来修复构象受损的蛋白质。因此，持有和催化去折叠伴侣蛋白可以作为主要的细胞防御机制，防止早期错误折叠和聚集的蛋白毒性构象的形成，以避免或延缓退行性蛋白构象疾病的发生。
By virtue of their general ability to bind (hold) translocating or unfolding polypeptides otherwise doomed to aggregate, molecular chaperones are commonly dubbed “holdases”. Yet, chaperones also carry physiological functions that do not necessitate prevention of aggregation, such as altering the native states of proteins, as in the disassembly of SNARE complexes and clathrin coats. To carry such physiological functions, major members of the Hsp70, Hsp110, Hsp100, and Hsp60/CCT chaperone families act as catalytic unfolding enzymes or unfoldases that drive iterative cycles of protein binding, unfolding/pulling, and release. One unfoldase chaperone may thus successively convert many misfolded or alternatively folded polypeptide substrates into transiently unfolded intermediates, which, once released, can spontaneously refold into low-affinity native products. Whereas during stress, a large excess of non-catalytic chaperones in holding mode may optimally prevent protein aggregation, after the stress, catalytic disaggregases and unfoldases may act as nanomachines that use the energy of ATP hydrolysis to repair proteins with compromised conformations. Thus, holding and catalytic unfolding chaperones can act as primary cellular defenses against the formation of early misfolded and aggregated proteotoxic conformers in order to avert or retard the onset of degenerative protein conformational diseases.
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