| 配分額 *注記 |
45,760千円 (直接経費: 35,200千円、間接経費: 10,560千円)
2024年度: 6,500千円 (直接経費: 5,000千円、間接経費: 1,500千円)
2023年度: 6,500千円 (直接経費: 5,000千円、間接経費: 1,500千円)
2022年度: 6,500千円 (直接経費: 5,000千円、間接経費: 1,500千円)
2021年度: 6,500千円 (直接経費: 5,000千円、間接経費: 1,500千円)
2020年度: 19,760千円 (直接経費: 15,200千円、間接経費: 4,560千円)
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| 研究実績の概要 |
We have made significant progress in three areas:
1) Asgard Tubulin: We have demonstrated that this protein is an intermediate between eukaryotic microtubules and the prokaryotic cell division machinery FtsZ. This provides a fascinating insight as to how a complex protein machine can evolve from a protein with a different function. These data were published in 2022.
Akil, C., Ali, S., Tran, L. T., Gaillard, J., Li, W., Hayashida, K., Hirose, M., Kato, T., Oshima, A., Fujishima, K., Blanchoin, L., Narita, A. & Robinson, R. C. Structure and dynamics of Odinarchaeota tubulin and the implications for eukaryotic microtubule evolution. Sci. Adv. (2022) 8, 10.1126/sciadv.abm2225
2) Heimdallarchaeota and Odinarchaeota gelsolins. Here we have demonstrated that gelolins from these to phyla are able to sever actin filaments in a calcium-dependent manner. This leads us to the conclusion that calcium signaling to the actin cytoskeleton was present in the last common ancestor of Asgard archaea and eukaryotes, and thus predate eukaryogenesis. This manuscript is under revision at PNAS.
3) Small GTPase signaling complexes. We have solved crystal structures of a Rab-like GTPase, several roadblock proteins and TRAPP proteins. These data allow us to demonstrate that the core proteins in eukaryotic signaling proteins, such as the ragulator complex, are present in Asgard archaea. Thus complex signalling to membranes predates eukaryogenesis. This manuscript is near completion.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
1: 当初の計画以上に進展している
理由
Our progress is on track at this stage of the grant. We have published and have generated significant interest in our Asgard Tubulin work. This is evinced by more than 2000 downloads of this manuscript following publication. Besides the research achievements listed above, we have made significant progress in other areas of eukaryotic-like proteins from Asgard archaea. In particular, we have crystal structures of parts of several parts of protein machine that are thought to be involved in membrane remodeling and in N-glycosylation pathways. These include BAR domain proteins, which in eukaryotes are able to produce membrane tubules. We have solve the structure of an ESCRT protein which is involved in membrane budding into vesicles in eukaryotes. Finally, we have solved a structure of a domain from an Asgard ribophorin a protein involved in N-glycosylation of newly synthesized proteins in eukaryotes. We aim to build these advances into complete stories during the forthcoming year.
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| 今後の研究の推進方策 |
The release of AlphaFold2, a deep-learning-aided, open-source protein structure prediction program, from DeepMind, opened a new era of molecular biology. The astonishing improvement in the accuracy of the structure predictions provides the opportunity to characterize systems from uncultured Asgard archaea, key organisms in evolutionary biology. Despite the accumulation in metagenomics-derived Asgard archaea eukaryotic-like sequences, limited structural and biochemical information have restricted the scope of our insight in their potential functions. We will integrate AlphaFold2 predictions with our structural biology and biochemistry to expand the targets of eukaryotic-like proteins that we study from Asgard archaea. In particular, we will use these predictions to help identify protein complexes that can be studied in vitro. This is important, since only one Asgard archaea has been isolated to date, and it is difficult to study due to its small size and slow growth rates. We expect this methodology to add a new dimension to our insight into eukaryogenesis.
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