Structural features of the GroEL-GroES nano-cage required for rapid folding of encapsulated protein
Structural features of the GroEL-GroES nano-cage required for rapid folding of encapsulated protein
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DOI：
10.1016/j.cell.2006.04.027
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发表时间：
2006-06-02
期刊：
影响因子：
64.5
通讯作者：
Hayer-Hartl, Manajit
中科院分区：
文献类型：
--
作者：
Tang, Yun-Chi;Chang, Hung-Chun;Hayer-Hartl, Manajit
GroEL和GroES形成分子伴侣蛋白纳米笼，使高达60 kDa的蛋白质在分离时折叠。在这里，我们探讨的结构特征的伴侣蛋白笼的快速折叠封装基板的关键。根据限制理论，调制GroEL中心腔的体积影响折叠速度。随着笼的尺寸逐渐减小到空间限制显著减缓折叠的程度，小蛋白（类似于30 kDa）折叠得更快。对于较大的蛋白质（类似于40-50 kDa），无论是扩大或减少笼体积减速折叠。此外，一些蛋白质的快速折叠需要与GroEL的C-末端、轻度疏水的Gly-Gly-Met重复序列的相互作用以及来自带负电荷的腔壁的排斥作用。我们认为，通过结合这些功能，伴侣蛋白笼提供了一个物理环境优化催化蛋白质的结构退火与动力学复杂的折叠途径。
GroEL and GroES form a chaperonin nano-cage for proteins up to similar to 60 kDa to fold in isolation. Here we explored the structural features of the chaperonin cage critical for rapid folding of encapsulated substrates. Modulating the volume of the GroEL central cavity affected folding speed in accordance with confinement theory. Small proteins (similar to 30 kDa) folded more rapidly as the size of the cage was gradually reduced to a point where restriction in space slowed folding dramatically. For larger proteins (similar to 40-50 kDa), either expanding or reducing cage volume decelerated folding. Additionally, interactions with the C-terminal, mildly hydrophobic Gly-Gly-Met repeat sequences of GroEL protruding into the cavity, and repulsion effects from the negatively charged cavity wall were required for rapid folding of some proteins. We suggest that by combining these features, the chaperonin cage provides a physical environment optimized to catalyze the structural annealing of proteins with kinetically complex folding pathways.