The Folding Mechanism of BBL: Plasticity of Transition-State Structure Observed within an Ultrafast Folding Protein Family
The Folding Mechanism of BBL: Plasticity of Transition-State Structure Observed within an Ultrafast Folding Protein Family
复制标题
DOI：
10.1016/j.jmb.2009.05.011
复制
发表时间：
2009-07-31
影响因子：
5.6
通讯作者：
Fersht, Alan R.
中科院分区：
文献类型：
--
作者：
Neuweiler, Hannes;Sharpe, Timothy D.;Fersht, Alan R.
对具有相似结构但不同序列的蛋白质家族成员的研究提供了对序列组成对折叠机制的影响的见解。外周亚单位结合结构域（PSBD）家族的成员折叠超快，并接近最小的尺寸为合作折叠蛋白质。PSBD E3 BD和POB的Phi值分析揭示了通过结构非常相似的极化过渡态通过成核-凝聚进行的折叠。在这里，我们提出了一个Phi值分析的家庭成员BBL，发现它也折叠成核-缩合机制。BBL、E3 BD和POB的平均Phi值接近相同，表明在过渡态中形成了相似的非共价相互作用部分。尽管在这个蛋白质家族的折叠机制的整体保守，然而，模式的Phi值确定BBL揭示了一个更大的分散的折叠核在整个结构，过渡态是较少的极化。所观察到的过渡态结构的可塑性可以合理化的PSBD序列的不同的螺旋形成倾向。BBL的第一螺旋中的非常强的螺旋倾向，相对于E3 BD和POB，似乎以第二螺旋中较弱的相互作用为代价，在过渡态的该螺旋中招募更多的结构形成。序列组成的差异可以调节甚至最小的天然蛋白质结构域的过渡态结构。(C)2009爱思唯尔有限公司保留所有权利。
Studies on members of protein families with similar structures but divergent sequences provide insights into the effects of sequence composition on the mechanism of folding. Members of the peripheral subunit-binding domain (PSBD) family fold ultrafast and approach the smallest size for cooperatively folding proteins. Phi-Value analysis of the PSBDs E3BD and POB reveals folding via nucleation-condensation through structurally very similar, polarized transition states. Here, we present a Phi-value analysis of the family member BBL and found that it also folds by a nucleation-condensation mechanism. The mean Phi values of BBL, E3BD, and POB were near identical, indicating similar fractions of non-covalent interactions being formed in the transition state. Despite the overall conservation of folding mechanism in this protein family, however, the pattern of Phi values determined for BBL revealed a larger dispersion of the folding nucleus across the entire structure, and the transition state was less polarized. The observed plasticity of transition-state structure can be rationalized by the different helix-forming propensities of PSBD sequences. The very strong helix propensity in the first helix of BBL, relative to E3BD and POB, appears to recruit more structure formation in that helix in the transition state at the expense of weaker interactions in the second helix. Differences in sequence composition can modulate transition-state structure of even the smallest natural protein domains. (C) 2009 Elsevier Ltd. All rights reserved.