Kinetic partitioning of protein folding and aggregation
Kinetic partitioning of protein folding and aggregation
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DOI：
10.1038/nsb752
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发表时间：
2002-02-01
期刊：
影响因子：
--
通讯作者：
Dobson, CM
中科院分区：
文献类型：
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作者：
Chiti, F;Taddei, N;Dobson, CM
我们系统地研究了40个单点突变对α/β蛋白酰基磷酸酶（AcP）变性形式转化为不溶性聚集体的影响。所有显著干扰聚集速率的突变都位于蛋白质序列的两个区域，残基16-31和87-98，每个区域具有相对高的疏水性和形成β-折叠结构的倾向。突变后测量的聚集速率的变化与突变所在的蛋白质区域的疏水性和β-折叠倾向的变化相关。决定聚集速率的蛋白质序列的两个区域不同于决定蛋白质折叠速率的序列的那些部分。将蛋白质解剖成对应于序列的不同区域的六个肽表明聚集和折叠之间的动力学分区可以归因于变性多肽链的固有构象偏好。
We have systematically studied the effects of 40 single point mutations on the conversion of the denatured form of the alpha/beta protein acylphosphatase (AcP) into insoluble aggregates. All the mutations that significantly perturb the rate of aggregation are located in two regions of the protein sequence, residues 16-31 and 87-98, each of which has a relatively high hydrophobicity and propensity to form beta-sheet structure. The measured changes in aggregation rate upon mutation correlate with changes in the hydrophobicity and beta-sheet propensity of the regions of the protein in which the mutations are located. The two regions of the protein sequence that determine the aggregation rate are distinct from those parts of the sequence that determine the rate of protein folding. Dissection of the protein into six peptides corresponding to different regions of the sequence indicates that the kinetic partitioning between aggregation and folding can be attributed to the intrinsic conformational preferences of the denatured polypeptide chain.