Potential new tools
Nature is full of potential useful tools. Proteins that can do tricks that we find useful or handy. But to use those potential tools optimally requires understanding of how they do the tricks they do. That is why British researchers set to find this out for the potential new protein tool SAP05
SAP05 originates from a bacterium. And is used by said bacterium to infect plants, and to transform them in a kind of zombie. This protein is regulating the directed degradation of a group of proteins who are involved in the switching on and off of developmental genes. Normally directed degradation only takes place when the protein to be degraded is decorated with the correct type of label. But SAP05 is skipping this step. And this is what is making SAP05 a potential tool.
But first it is required to find out how precisely SAP05 is doing this. Therefor the researchers determined its structure. This they did with SAP05 bound to either its degradation target protein, or to a protein of degradation machinery. finding out that SAP05 is a compact globular protein, with a binding place for the soon to be degraded protein at one side, and at the opposite side a binding place for the protein of the degradation machinery.
It is possible to adapt SAP05 in such a way that we can control which proteins it binds
Subsequently the researchers created mutations at the discovered protein binding places. In this way they learn more about the specific protein binding spots. They discovered that a single mutation could be enough to disrupt the binding of the soon to be degraded protein. Showing that the binding with the to be degraded protein is not strong. But still specific.
In contrast, the binding with the protein of the degradation machinery was more robust. Possible, so suggest the researchers because a weaker binding can result in that SAP05 will be degraded together with its target protein.
In addition, the researchers made models of SAP05 together with the whole protein degradation machinery. These like to suggest that SAP05 is positioned in such a way that the soon to be degraded protein bound to SAP05 is automatically shuffled into the degradation machinery.
This research shows how SAP05 works. And that it is possible to adapt SAP05 in such a way that we can control which proteins it binds. Giving SAP05 potential therapeutic uses say the researchers.
Literature
Qun Liu, Abbas Maqbool, Federico G. Mirkin, Yeshveer Singh, Clare E. M. Stevenson, David M. Lawson, Sophien Kamoun, Weijie Huang, Saskia A. Hogenhout (2023) Bimodular architecture of bacterial effector SAP05 that drives ubiquitin-independent targeted protein degradation. PNAS: 120 (49) e2310664120 https://doi.org/10.1073/pnas.2310664120
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