小柯机器人

德国欧洲分子生物学实验室Mikhail M. Savitski、Athanasios Typas等研究人员合作首次绘制出大肠杆菌的功能蛋白质图谱。相关论文于2020年12月9日在线发表在《自然》杂志上。

通过使用高含量的生化读数、热蛋白质组图谱，研究人员在大肠杆菌中测量了应对121中遗传扰动时蛋白质组范围的蛋白质丰度和热稳定性。结果表明，热稳定性以及必需蛋白质的状态和相互作用通常受到调节，从而提高了研究蛋白质组的可能性。研究人员发现，功能相关的蛋白质由于它们的共同调节和物理相互作用（与蛋白质、代谢物或辅因子），在整个扰动中具有协调的丰度和热稳定性变化。最后，研究人员提供对已知生长表型的机制见解。这些数据能够作为推测蛋白质功能和相互作用的丰富资源。

据悉，高通量反向遗传学的最新进展彻底改变了人们定位基因功能和相互作用的能力。这些方法的能力取决于它们识别功能相关基因的能力，这些基因在敲除后会在几种扰动（化学、环境或遗传）中引发相似的表型变化。但是，由于存在大量扰动，这些方法仅限于生长或形态学读数。

附：英文原文

Title: The functional proteome landscape of Escherichia coli

Author: Andr Mateus, Johannes Hevler, Jacob Bobonis, Nils Kurzawa, Malay Shah, Karin Mitosch, Camille V. Goemans, Dominic Helm, Frank Stein, Athanasios Typas, Mikhail M. Savitski

Issue&Volume: 2020-12-09

Abstract: Recent developments in high-throughput reverse genetics1,2 have revolutionized our ability to map gene function and interactions3,4,5,6. The power of these approaches depends on their ability to identify functionally associated genes, which elicit similar phenotypic changes across several perturbations (chemical, environmental or genetic) when knocked out7,8,9. However, owing to the large number of perturbations, these approaches have been limited to growth or morphological readouts10. Here we use a high-content biochemical readout, thermal proteome profiling11, to measure the proteome-wide protein abundance and thermal stability in response to 121 genetic perturbations in Escherichia coli. We show that thermal stability, and therefore the state and interactions of essential proteins, is commonly modulated, raising the possibility of studying a protein group that is particularly inaccessible to genetics. We find that functionally associated proteins have coordinated changes in abundance and thermal stability across perturbations, owing to their co-regulation and physical interactions (with proteins, metabolites or cofactors). Finally, we provide mechanistic insights into previously determined growth phenotypes12 that go beyond the deleted gene. These data represent a rich resource for inferring protein functions and interactions.

DOI: 10.1038/s41586-020-3002-5

Source: https://www.nature.com/articles/s41586-020-3002-5

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html