page_title: Protein complex
section_title: Essential proteins in protein complexes
hierarchical_section_title: Protein complex / Essential proteins in protein complexes
caption_attribution_description: English: Distribution of essential genes among complexes in S. cerevisiae. Essential genes are shown in red, nonessential in blue. Redrawn after Figure 1 in Ryan et al. 2013
context_page_description: A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Different polypeptide chains may have different functions. This is distinct from a multienzyme complex, in which multiple catalytic domains are found in a single polypeptide chain.
  Protein complexes are a form of quaternary structure. Proteins in a protein complex are linked by non-covalent protein–protein interactions, and different protein complexes have different degrees of stability over time. These complexes are a cornerstone of many biological processes and together they form various types of molecular machinery that perform a vast array of biological functions. The cell is seen to be composed of modular supramolecular complexes, each of which performs an independent, discrete biological function.
  Through proximity, the speed and selectivity of binding interactions between enzymatic complex and substrates can be vastly improved, leading to higher cellular efficiency. Many of the techniques used to break open cells and isolate proteins are inherently disruptive to such large complexes, so it is often difficult to determine the components of a complex.
context_section_description: Although some early studies  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). However, the correlation is robust for networks of stable co-complex interactions. In fact, a disproportionate number of essential genes belong to protein complexes. This led to the conclusion that essentiality is a property of molecular machines (i.e. complexes) rather than individual components. 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. Ryan et al. (2013) referred to the observation that entire complexes appear essential as "modular essentiality". 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.
  In humans, genes whose protein products belong to the same complex are more likely to result in the same disease phenotype.
caption: Essential proteins in yeast complexes occur much less randomly than expected by chance. Modified after Ryan et al. 2013[10]
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