Apparent cooperativity in the folding of multidomain proteins depends on the relative rates of folding of the constituent domains
Apparent cooperativity in the folding of multidomain proteins depends on the relative rates of folding of the constituent domains
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DOI：
10.1073/pnas.0604580103
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发表时间：
2006-11-28
影响因子：
11.1
通讯作者：
Clarke, Jane
中科院分区：
文献类型：
--
作者：
Batey, Sarah;Clarke, Jane
大约75%的真核生物蛋白质含有一个以上的所谓独立折叠结构域。然而，有相对较少的系统研究，以探讨结构域间的相互作用对蛋白质的稳定性和折叠动力学的影响更少。我们提出的折叠对三螺旋束血影蛋白域作为一个范例，以表明如何复杂的分析可以。平衡研究表明，只有一个单一的展开过渡展开的结构域所需的变性剂浓度的增加，然而，在某些情况下，这是不伴随着m值的增加，这将是预期的，如果蛋白质是一个真正的合作，全有或全无系统。我们分析了血影蛋白结构域对，野生型和精心挑选的突变体的复杂动力学。通过比较这些对，我们能够证明，平衡数据本身是不足以描述多结构域蛋白质的折叠和量化的影响，一个域可以对其邻居。
Approximately 75% of eukaryotic proteins contain more than one so-called independently folding domain. However, there have been relatively few systematic studies to investigate the effect of interdomain interactions on protein stability and fewer still on folding kinetics. We present the folding of pairs of three-helix bundle spectrin domains as a paradigm to indicate how complex such an analysis can be. Equilibrium studies show an increase in denaturant concentration required to unfold the domains with only a single unfolding transition; however, in some cases, this is not accompanied by the increase in m value, which would be expected if the protein is a truly cooperative, all-or-none system. We analyze the complex kinetics of spectrin domain pairs, both wild-type and carefully selected mutants. By comparing these pairs, we are able to demonstrate that equilibrium data alone are insufficient to describe the folding of multidomain proteins and to quantify the effects that one domain can have on its neighbor.