研究・研究者
研究会・セミナー
| 演 題 | 「Biological Phase Transitions: Where Chemistry and Physics Meet Biology」 |
|---|---|
| 日 時 | 2024年10月25日(金) 16:00 より 17:00 まで |
| 講演者 | Samrat Mukhopadhyay教授（Indian Institute of Science Education and Research, Mohali） |
| 場 所 | 山手キャンパス2号館2階 山手サロン |
| 概 要 | プリオンタンパク質の液‒液相分離（liquid‒liquid phase separation：LLPS）現象についてご講演頂きます。Mukhopadhyay教授は、米国生物物理学会のBiophysical Journalのエディターも務めておられる非常にアクティブな研究者です。皆様のご参加を歓迎致します。 要旨：Cells contain membrane-enclosed organelles that compartmentalize cellular constituents and regulate biochemical processes. A growing body of exciting research now reveals that there is also an alternative mechanism of spatiotemporally-controlled intracellular compartmentalization and organization through biomolecular condensate formation via macromolecular phase separation of proteins and nucleic acids into noncanonical membraneless organelles with emergent material properties. These functional liquid-like biomolecular condensates can undergo aberrant irreversible phase transitions into gel-like or solid-like amyloid aggregates associated with a range of debilitating human diseases [1,2]. Our longstanding interest in prion biology led us to discover that the prion protein (PrP) (well-known for its association with mad cow disease and Creutzfeldt-Jakob disease) can undergo phase separation via weak, multivalent, transient intermolecular interactions between the N-terminal domain. An intriguing disease-associated amber stop codon mutation (Y145Stop) of PrP yields a C-terminally truncated intrinsically disordered fragment. We demonstrated that this fragment spontaneously phase-separates into highly dynamic liquid droplets under physiological conditions [3]. Upon aging, these liquid droplets undergo a liquid-to-solid phase transition into highly ordered, b-rich, amyloid-like aggregates that exhibit a characteristic autocatalytic self-templating behavior. The propensity for the aberrant phase transition is much lower for the full-length PrP indicating an evolutionarily conserved role of the folded C-terminal domain. Our recent results also showed intriguing spatiotemporal modulations in complex coacervation of PrP with other neuronal intrinsically disordered proteins into heterotypic, multi-component, multiphasic, multilayered condensates in the presence of RNA [4,5]. I will also discuss our surface-enhanced Raman scattering (SERS), single-molecule FRET (Förster resonance energy transfer), and homoFRET studies that capture exquisite molecular details of in-vitro-reconstituted biomolecular condensates and cellular stress granules derived from neuronal RNA-binding proteins that are associated with Amyotrophic Lateral Sclerosis [6-8].
1. Mukhopadhyay Nature Chemistry (News & Views) (2021) 13, 1028-1030. |
| お問合せ先 | 飯野亮太（生命・錯体分子科学研究領域、iino[at]ims.ac.jp（[at]は＠に変換してください。）） |
