Chaperone rings in protein folding and degradation
Chaperone rings in protein folding and degradation
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DOI：
10.1073/pnas.96.20.11033
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发表时间：
1999-09-28
影响因子：
11.1
通讯作者：
Finley, D
中科院分区：
文献类型：
--
作者：
Horwich, AL;Weber-Ban, EU;Finley, D
伴侣环在许多细胞蛋白质的折叠和降解的相反ATP介导的过程中起着至关重要的作用，但是它们帮助这些生命和死亡作用的机制才刚刚开始被理解。环结构对这两个过程都具有优势，提供了中央空腔内底物蛋白质的区室化，在基质和高局部浓度的结合位点之间可能发生潜在的协同相互作用，而其它蛋白质进入空腔的途径在空间上受到限制。这种限制防止了可能导致底物蛋白以非天然形式存在时的非生产性结局的外部干扰，例如聚集。在识别步骤中，伴侣环识别其底物中的不同基序，在蛋白质折叠伴侣蛋白的情况下识别暴露的疏水性，并且在蛋白水解伴侣蛋白的至少一些情况下识别特异性“标签”序列。对于折叠复合物和蛋白水解复合物，ATP指导分子伴侣环中的构象变化，所述分子伴侣环控制结合多肽的释放。在伴侣蛋白的情况下，ATP使释放的蛋白质能够在隔离的亲水性折叠室中追求天然状态，并且在蛋白酶的情况下，释放的多肽易位到降解室中。这些不同的命运至少部分地由与伴侣环相关的非常不同的合作成分决定：即一方面是辅伴侣环，另一方面是蛋白水解环组装体。在这里，我们回顾了两种类型的结构和机制伴侣环系统。
Chaperone rings play a vital role in the opposing ATP-mediated processes of folding and degradation of many cellular proteins, but the mechanisms by which they assist these life and death actions are only beginning to be understood, Ring structures present an advantage to both processes, providing for compartmentalization of the substrate protein inside a central cavity in which multivalent, potentially cooperative interactions can take place between the substrate and a high local concentration of binding sites, while access of other proteins to the cavity is restricted sterically. Such restriction prevents outside interference that could lead to nonproductive fates of the substrate protein while it is present in non-native form, such as aggregation. At the step of recognition, chaperone rings recognize different motifs in their substrates, exposed hydrophobicity in the case of protein-folding chaperonins, and specific "tag" sequences in at least some cases of the proteolytic chaperones. For both folding and proteolytic complexes, ATP directs conformational changes in the chaperone rings that govern release of the bound polypeptide. In the case of chaperonins, ATP enables a released protein to pursue the native state in a sequestered hydrophilic folding chamber, and, in the case of the proteases, the released polypeptide is translocated into a degradation chamber. These divergent fates are at least partly governed by very different cooperating components that associate with the chaperone rings: that is, cochaperonin rings on one hand and proteolytic ring assemblies on the other, Here we review the structures and mechanisms of the two types of chaperone ring system.