タンパク質過剰に関する新研究 (Protein Overabundance Study)

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2026-04-22 ワシントン大学(UW)

米国のUniversity of Washingtonの研究チームは、細胞内でタンパク質が過剰に存在することの影響を解明した。従来はタンパク質の不足が主に問題視されてきたが、本研究は「過剰」も細胞機能に深刻な影響を与えることを示した。特に、過剰なタンパク質が細胞内のバランスを乱し、分子間相互作用や生理機能を阻害する可能性が明らかとなった。これにより、細胞は適切なタンパク質濃度を維持する必要があることが強調される。こうした知見は、がんや神経変性疾患など、タンパク質制御異常に関連する疾患の理解や治療戦略の開発に貢献すると期待される。

タンパク質過剰に関する新研究 (Protein Overabundance Study)
In a new study, UW researchers explored why cells “stockpile” some proteins that are required for growth. Shown here is a series of “heat map” images that detail the abundance of a required protein over five bacterial generations — red represents more protein within the cell, while dark blue represents less. When the researchers disabled the gene necessary to make the protein, the abundance of that protein diminished in each generation (top row). The cells in the bottom row had a functioning gene, so the protein remained abundant. Photo: H. James Cho et. al/Science Advances

<関連情報>

タンパク質の過剰は成長の頑健性によって引き起こされる Protein overabundance is driven by growth robustness

H. James Choi, Teresa W. Lo, Kevin J. Cutler, Dean Huang, […] , and Paul A. Wiggins
Science Advances   Published:20 Mar 2026
DOI:https://doi.org/10.1126/sciadv.adz9623

Abstract

Protein expression levels optimize cell fitness: Too low an expression level of essential proteins will slow growth by compromising essential processes, whereas overexpression slows growth by increasing the metabolic load. This trade-off naïvely predicts that cells maximize their fitness by sufficiency, expressing just enough of each essential protein for function. We test this prediction in the naturally competent bacterium Acinetobacter baylyi by characterizing the proliferation dynamics of essential-gene knockouts at a single-cell scale (by imaging) as well as at a genome-wide scale. In these experiments, cells proliferate for multiple generations as target protein levels are diluted from their endogenous levels. This approach facilitates a proteome-scale analysis of the fitness landscape with respect to protein abundance. We find that most essential proteins are subject to a threshold-like fitness landscape: Growth is independent of protein abundance above a critical threshold and arrests below that threshold. We have recently analyzed the implications of this landscape for growth robustness. Confirming signature predictions of this model, we find that (i) roughly 70% of essential proteins are overabundant, (ii) overabundance increases as the expression level decreases, and (iii) the lowest abundance proteins are in vast excess (>10×) of what is required for growth in the typical cell. These results reveal that robustness plays a fundamental role in determining the expression levels of essential genes and that overabundance is a key mechanism for ensuring robust growth.

生物化学工学
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