Alternative Protein-Protein Interfaces Are Frequent Exceptions
Alternative Protein-Protein Interfaces Are Frequent Exceptions
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DOI：
10.1371/journal.pcbi.1002623
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发表时间：
2012-08-01
影响因子：
4.3
通讯作者：
Rost, Burkhard
中科院分区：
文献类型：
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作者：
Hamp, Tobias;Rost, Burkhard
蛋白质-蛋白质相互作用（PPI）的复杂分子细节对功能至关重要。因此，再次测量相同的相互作用蛋白质对，我们预计会得到相同的结果。这项工作测量了不同实验之间相同和同源蛋白质对相互作用的分子细节的相似性。分析的所有分数表明，不同的实验经常在类似PPI的界面中发现例外：高达22%的比较显示出一些差异，即使是序列相同的蛋白质对。近缘同源物对的相应数量达到68%。相反，在所有比较中，12-29%的界面完全不同。所有这些估计都是在冗余减少后计算的。界面差异的大小从细微到极端不等，几个例子说明了这一点。一个极端的情况是在两个相同的生物相互作用的观察之间的相互作用域的变化。不同界面的一个原因是同一复合物中相互作用的拷贝数：观察到替代结合模式的概率随着拷贝数的增加而增加。即使在去除具有相同同聚物的替代异界面的特殊情况后，仍然存在很大的可变性。我们的研究结果有力地支持了一个令人惊讶的观点，即有许多替代方案可以使PPI的复杂分子细节对功能至关重要。
The intricate molecular details of protein-protein interactions (PPIs) are crucial for function. Therefore, measuring the same interacting protein pair again, we expect the same result. This work measured the similarity in the molecular details of interaction for the same and for homologous protein pairs between different experiments. All scores analyzed suggested that different experiments often find exceptions in the interfaces of similar PPIs: up to 22% of all comparisons revealed some differences even for sequence-identical pairs of proteins. The corresponding number for pairs of close homologs reached 68%. Conversely, the interfaces differed entirely for 12-29% of all comparisons. All these estimates were calculated after redundancy reduction. The magnitude of interface differences ranged from subtle to the extreme, as illustrated by a few examples. An extreme case was a change of the interacting domains between two observations of the same biological interaction. One reason for different interfaces was the number of copies of an interaction in the same complex: the probability of observing alternative binding modes increases with the number of copies. Even after removing the special cases with alternative hetero-interfaces to the same homomer, a substantial variability remained. Our results strongly support the surprising notion that there are many alternative solutions to make the intricate molecular details of PPIs crucial for function.