Evolutionary and physiological importance of hub proteins.
Evolutionary and physiological importance of hub proteins.
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DOI：
10.1371/journal.pcbi.0020088
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发表时间：
2006-07-14
影响因子：
4.3
通讯作者：
Tyers M
中科院分区：
文献类型：
--
作者：
Batada NN;Hurst LD;Tyers M
已经声称具有更多相互作用伴侣（枢纽）的蛋白质在生理上更重要（即，更少），并且由于假定的高密度结合位点，进化缓慢。然而，并不是所有的分析都支持这些结果，可能是因为有偏见和不太可靠的全球蛋白质相互作用数据。在这里，我们提供了这些问题的第一次检查使用一个全面的文献策划的数据集充分证实的蛋白质相互作用的酿酒酵母。虽然单独使用不太可靠的酵母双杂交数据可以拒绝局部连接性与可分配性度量相关的可能性，但在更高质量的数据集中观察到相对稳健的相关性。相比之下，即使在可靠的数据集中，局部连接性也与蛋白质进化的速率无关。这种可能令人惊讶的缺乏与进化速率的相关性似乎部分是由于枢纽蛋白没有更高密度的与结合相关的残基。然而，枢纽蛋白至少有一组其他不寻常的功能，即快速周转和调节，表现在高mRNA衰变率和大量的磷酸化位点。我们认为，这是一种适应，以尽量减少不必要的激活途径，可能介导的外源结合枢纽，他们积极坚持比所需的时间在任何给定的时间点。我们的结论是，枢纽蛋白是更重要的细胞生长速度和严格的监管下，但不是缓慢的演变。为什么有些蛋白质进化得如此缓慢？为什么只有少数蛋白质对生物体的功能至关重要？了解蛋白质如何与其他蛋白质相互作用可能会提供答案。有人认为，有些蛋白质就像一个轮子上的轮毂，上面附着着多个辐条（相互作用的伙伴）：去掉一个辐条，轮子就能工作，去掉轮毂，轮子就没用了。有这么多的蛋白质结合，枢纽也可能是缓慢的演变，因为一些相互作用的网站是在他们的进化受到限制。不幸的是，以前的分析一直是模棱两可的，尤其是因为不确定哪些蛋白质与哪些蛋白质相互作用。在这里，作者采用了广泛的文献策划的可靠蛋白质-蛋白质相互作用的数据集来解决必要性，连接性和进化速率的问题。这项研究发现，枢纽更有可能是必不可少的，如果不是必不可少的，至少对健身有更大的影响。然而，枢纽蛋白的进化并不缓慢，部分原因是枢纽蛋白没有更高密度的结合位点。然而，枢纽蛋白似乎受到了强烈的调节，作者认为这种适应可以最大限度地减少不必要的激活风险。
It has been claimed that proteins with more interaction partners (hubs) are both physiologically more important (i.e., less dispensable) and, owing to an assumed high density of binding sites, slow evolving. Not all analyses, however, support these results, probably because of biased and less-than reliable global protein interaction data. Here we provide the first examination of these issues using a comprehensive literature-curated dataset of well-substantiated protein interactions in Saccharomyces cerevisiae. Whereas use of less reliable yeast two-hybrid data alone can reject the possibility that local connectivity correlates with measures of dispensability, in higher quality datasets a relatively robust correlation is observed. In contrast, local connectivity does not correlate with the rate of protein evolution even in reliable datasets. This perhaps surprising lack of correlation with evolutionary rate appears in part to arise from the fact that hub proteins do not have a higher density of residues associated with binding. However, hub proteins do have at least one other set of unusual features, namely rapid turnover and regulation, as manifest in high mRNA decay rates and a large number of phosphorylation sites. This, we suggest, is an adaptation to minimize unwanted activation of pathways that might be mediated by adventitious binding to hubs, were they to actively persist longer than required at any given time point. We conclude that hub proteins are more important for cellular growth rate and under tight regulation but are not slow evolving. Why do some proteins evolve so very slowly? Why are only a few proteins uniquely vital to the functioning of an organism? Understanding how proteins interact with other proteins may provide the answers. Some proteins are, it is suggested, like hubs on a wheel with multiple spokes (interacting partners) attached: take away a spoke and the wheel works, take away the hub and the wheel is useless. With so many proteins to bind with, hubs may also be as slow evolving as some interaction sites are constrained in their evolution. Unfortunately, prior analyses have been equivocal, not least because of an uncertainty about which proteins interact with which others. Here the authors employ an extensive literature-curated dataset of reliable protein–protein interactions to address the issue of essentiality, connectivity, and evolutionary rate. This study finds that hubs are more likely to be essential, and if not essential, at least have a larger impact on fitness. However, hub proteins are not slow evolving, in part, because hubs do not have a higher density of binding sites. Hub proteins do, however, appear to be under strong regulation, an adaptation the authors suggest that minimizes the risk of unwanted activation.
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影响因子：
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