The Subunit Interfaces of Weakly Associated Homodimeric Proteins
The Subunit Interfaces of Weakly Associated Homodimeric Proteins
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DOI：
10.1016/j.jmb.2010.02.020
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发表时间：
2010-04-23
影响因子：
5.6
通讯作者：
Janin, Joel
中科院分区：
文献类型：
--
作者：
Dey, Sucharita;Pal, Arumay;Janin, Joel
我们分析了315个同源二聚体的亚基界面与蛋白质数据库中的X射线结构，通过检查文献中的数据进行验证，表明蛋白质在溶液中是二聚体，并且在“弱”二聚体的情况下，同源二聚体与单体处于平衡状态。42个弱二聚体的界面，平均比该组的其余部分小2.4倍，与抗体-抗原或蛋白酶-抑制剂界面的尺寸相当。尽管如此，它们比平均瞬时蛋白质-蛋白质复合物更具疏水性，并且在氨基酸组成上与其他同二聚体界面相似。在同二聚体和瞬时复合物中，每单位面积的界面氢键和水合水分子的平均数也相似。与原子包装相关的参数表明，许多弱二聚体接口是松散的包装，我们建议，这有助于他们的低稳定性。为了评估界面残基上的进化选择压力，我们计算了同源氨基酸序列在60%序列同一性下的香农熵。在93%的同源二聚体中，界面残基比蛋白质表面残基更保守。弱二聚体显示出与其他同源二聚体相同的高度界面保守性，但它们的同系物可能是异源二聚体以及同源二聚体。它们的接口可能是很好的模型，在其大小，组成和进化保守的不稳定的亚基接触，使蛋白质组装共享和交换组件，变构蛋白进行四级结构转换，和分子机器在细胞中运行。(C)2010爱思唯尔有限公司版权所有。
We analyzed subunit interfaces in 315 homodimers with an X-ray structure in the Protein Data Bank, validated by checking the literature for data that indicate that the proteins are dimeric in solution and that, in the case of the "weak" dimers, the homodimer is in equilibrium with the monomer. The interfaces of the 42 weak dimers, which are smaller by a factor of 2.4 on average than in the remainder of the set, are comparable in size with antibody-antigen or protease-inhibitor interfaces. Nevertheless, they are more hydrophobic than in the average transient protein-protein complex and similar in amino acid composition to the other homodimer interfaces. The mean numbers of interface hydrogen bonds and hydration water molecules per unit area are also similar in homodimers and transient complexes. Parameters related to the atomic packing suggest that many of the weak dimer interfaces are loosely packed, and we suggest that this contributes to their low stability. To evaluate the evolutionary selection pressure on interface residues, we calculated the Shannon entropy of homologous amino acid sequences at 60% sequence identity. In 93% of the homodimers, the interface residues are better conserved than the residues on the protein surface. The weak dimers display the same high degree of interface conservation as other homodimers, but their homologs may be heterodimers as well as homodimers. Their interfaces may be good models in terms of their size, composition, and evolutionary conservation for the labile subunit contacts that allow protein assemblies to share and exchange components, allosteric proteins to undergo quaternary structure transitions, and molecular machines to operate in the cell. (C) 2010 Elsevier Ltd. All rights reserved.