Protein chain collapse modulation and folding stimulation by GroEL-ES.
Protein chain collapse modulation and folding stimulation by GroEL-ES.
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DOI：
10.1126/sciadv.abl6293
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发表时间：
2022-03-04
期刊：
影响因子：
13.6
通讯作者：
Tans SJ
中科院分区：
文献类型：
--
作者：
Naqvi MM;Avellaneda MJ;Roth A;Koers EJ;Roland A;Sunderlikova V;Kramer G;Rye HS;Tans SJ
多肽的崩溃被认为是蛋白质折叠、聚集、内在无序和相分离的重要因素。然而，是否在细胞中调节多肽崩溃来控制蛋白质状态尚不清楚。在这里，使用集成的蛋白质操作和成像，我们证明了伴侣蛋白GroEL-ES可以通过加强蛋白质的崩溃来加速蛋白质的折叠。GroEL在底物链中诱导收缩力量，将它们吸引到空腔中，并触发一般的压缩和离散的折叠转变，即使对于缓慢折叠的蛋白质也是如此。这种塌陷增强在GroEL的核苷酸结合状态下最强，并得到与空腔边缘的GroES结合和空腔底部的两亲性C-末端尾巴的帮助。崩塌调制不同于其他已提出的GroEL-ES折叠加速机制，包括空间约束和错误折叠展开。鉴于崩溃在整个蛋白质组中的普遍存在，我们推测崩溃调制在蛋白质质量控制机制中更普遍地相关。多肽链的折叠在GroEL-ES空腔内增强，即使在折叠速度较慢的蛋白质中也会触发折叠。
The collapse of polypeptides is thought important to protein folding, aggregation, intrinsic disorder, and phase separation. However, whether polypeptide collapse is modulated in cells to control protein states is unclear. Here, using integrated protein manipulation and imaging, we show that the chaperonin GroEL-ES can accelerate the folding of proteins by strengthening their collapse. GroEL induces contractile forces in substrate chains, which draws them into the cavity and triggers a general compaction and discrete folding transitions, even for slow-folding proteins. This collapse enhancement is strongest in the nucleotide-bound states of GroEL and is aided by GroES binding to the cavity rim and by the amphiphilic C-terminal tails at the cavity bottom. Collapse modulation is distinct from other proposed GroEL-ES folding acceleration mechanisms, including steric confinement and misfold unfolding. Given the prevalence of collapse throughout the proteome, we conjecture that collapse modulation is more generally relevant within the protein quality control machinery. The collapse of polypeptide chains is enhanced inside the GroEL-ES cavity, which triggers folding even in slow-folding proteins.
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