Unexpected Effects of Macromolecular Crowding on Protein Stability
Unexpected Effects of Macromolecular Crowding on Protein Stability
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DOI：
10.1021/bi300909q
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发表时间：
2012-12-11
期刊：
影响因子：
2.9
通讯作者：
Pielak, Gary J.
中科院分区：
文献类型：
--
作者：
Benton, Laura A.;Smith, Austin E.;Pielak, Gary J.
大多数关于大分子拥挤的理论都集中在两个概念上：Crowder的大分子性质和熵。对于蛋白质，Crowder排除的体积有利于紧密的天然状态，而不是扩展的变性状态，通过降低展开熵来增强蛋白质的稳定性。我们用广泛使用的堵塞剂Ficoll-70及其单体蔗糖测试了这些想法。与预期相反，Ficoll和蔗糖对胰凝乳酶抑制剂2具有大致相同的稳定作用。此外，稳定作用是由焓而不是熵驱动的。这些结果表明，需要进行仔细的对照研究和更复杂的理论来理解拥挤效应。
Most theories about macromolecular crowding focus on two ideas: the macromolecular nature of the crowder and entropy. For proteins, the volume excluded by the crowder favors compact native states over expanded denatured states, enhancing protein stability by decreasing the entropy of unfolding. We tested these ideas with the widely used crowding agent Ficoll-70 and its monomer, sucrose. Contrary to expectations, Ficoll and sucrose have approximately the same stabilizing effect on chymotrypsin inhibitor 2. Furthermore, the stabilization is driven by enthalpy, not entropy. These results point to the need for carefully controlled studies and more sophisticated theories for understanding crowding effects.