Editing Protein complex (section)

== Essential proteins in protein complexes ==

[[Image:Essential proteins in yeast complexes.png|thumb|right|250px|Essential proteins in yeast complexes occur much less randomly than expected by chance. Modified after Ryan et al. 2013<ref name="Ryan2013"/>]]

Although some early studies<ref name="Jeong2001">{{Cite journal
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| year = 2001
| last1 = Jeong
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| title = Lethality and centrality in protein networks
| journal = Nature
| volume = 411
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}}</ref> suggested a strong correlation between essentiality and protein interaction degree (the "centrality-lethality" rule) subsequent analyses have shown that this correlation is weak for binary or transient interactions (e.g., [[Yeast two hybrid|yeast two-hybrid]]).<ref name="Yu2008">{{Cite journal
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}}</ref><ref name="Zotenko2008">{{Cite journal
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| title = Why do hubs in the yeast protein interaction network tend to be essential: Reexamining the connection between the network topology and essentiality
| journal = PLOS Computational Biology
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}}</ref> However, the correlation is robust for networks of stable co-complex interactions. In fact, a disproportionate number of [[essential genes]] belong to protein complexes.<ref name="Hart2007">{{Cite journal
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| year = 2007
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| title = A high-accuracy consensus map of yeast protein complexes reveals modular nature of gene essentiality
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}}</ref> This led to the conclusion that essentiality is a property of molecular machines (i.e. complexes) rather than individual components.<ref name="Hart2007"/> Wang et al. (2009) noted that larger protein complexes are more likely to be essential, explaining why essential genes are more likely to have high co-complex interaction degree.<ref name="Wang2009">{{Cite journal
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}}</ref> Ryan et al. (2013) referred to the observation that entire complexes appear essential as "'''modular essentiality'''".<ref name="Ryan2013">{{Cite journal
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| year = 2013
| last1 = Ryan
| first1 = C. J.
| title = All or nothing: Protein complexes flip essentiality between distantly related eukaryotes
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}}</ref> These authors also showed that complexes tend to be composed of either essential or non-essential proteins rather than showing a random distribution (see Figure). However, this not an all or nothing phenomenon: only about 26% (105/401) of yeast complexes consist of solely essential or solely nonessential subunits.<ref name="Ryan2013" />

In humans, genes whose protein products belong to the same complex are more likely to result in the same disease phenotype.<ref name="Fraser2007">{{Cite journal
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| title = Using protein complexes to predict phenotypic effects of gene mutation
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| title = A human phenome-interactome network of protein complexes implicated in genetic disorders
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| url = https://lirias.kuleuven.be/handle/123456789/74164
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| year = 2007
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| title = The modular nature of genetic diseases
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}}</ref>