Allosteric models for cooperative polymerization of linear polymers
Allosteric models for cooperative polymerization of linear polymers
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DOI：
10.1529/biophysj.107.126219
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发表时间：
2008-09-01
影响因子：
3.4
通讯作者：
Romberg, Laura
中科院分区：
文献类型：
--
作者：
Miraldi, Emily R.;Thomas, Peter J.;Romberg, Laura
在细胞骨架中，不利的成核步骤允许细胞调节聚合物组装的位置、时间和数量。成核聚合在传统上被解释为多链聚合物协同组装的模型，而线性的单链聚合物则不然。最近关于FtsZ（微管蛋白的细菌同系物）组装的数据不符合这两类。FtsZ可折叠成单链原蛋白。在没有横向相互作用的情况下是稳定的，但是它们协同组装。我们开发了一个合作聚合的模型，不需要聚合物是多链的。相反，构象变化允许低聚物中的亚基以高亲和力缔合，而低亲和力构象在单体中是有利的。我们推导出计算聚合物浓度，亚基构象，和亚基的聚合物末端的表观亲和力的方程。平衡常数的某些组合产生协同聚合的尖锐的临界浓度特征。在这些情况下，低亲和力构象在单体中占主导地位，而几乎所有的聚合物都由高亲和力亚基组成。我们的模型预测，形成HH二聚体的三种途径都涉及不稳定的中间体，限制成核。这里开发的数学框架可以表示具有各种生化解释的变构组装系统，其中一些可以显示协同性，而另一些则不能。
In the cytoskeleton, unfavorable nucleation steps allow cells to regulate where, when, and how many polymers assemble. Nucleated polymerization is traditionally explained by a model in which multistranded polymers assemble cooperatively, whereas linear, single-stranded polymers do not. Recent data on the assembly of FtsZ, the bacterial homolog of tubulin, do not fit either category. FtsZ can polymerize into single-stranded proto. laments that are stable in the absence of lateral interactions, but that assemble cooperatively. We developed a model for cooperative polymerization that does not require polymers to be multistranded. Instead, a conformational change allows subunits in oligomers to associate with high affinity, whereas a lower-affinity conformation is favored in monomers. We derive equations for calculating polymer concentrations, subunit conformations, and the apparent affinity of subunits for polymer ends. Certain combinations of equilibrium constants produce the sharp critical concentrations characteristic of cooperative polymerization. In these cases, the low-affinity conformation predominates in monomers, whereas virtually all polymers are composed of high-affinity subunits. Our model predicts that the three routes to forming HH dimers all involve unstable intermediates, limiting nucleation. The mathematical framework developed here can represent allosteric assembly systems with a variety of biochemical interpretations, some of which can show cooperativity, and others of which cannot.