Title Controlling synthetic membraneless organelles by a red-light-dependent singlet oxygen-generating protein
Authors Li, Manjia
Park, Byung Min
Dai, Xin
Xu, Yingjie
Huang, Jinqing
Sun, Fei
Affiliation Hong Kong Univ Sci & Technol, Dept Chem & Biol Engn, Kowloon, Clear Water Bay, Hong Kong, Peoples R China
Hong Kong Univ Sci & Technol, Dept Chem, Kowloon, Clear Water Bay, Hong Kong, Peoples R China
Hlth InnoHK, Lab Synthet Chem & Chem Biol, Hong Kong Sci Pk, Hong Kong, Peoples R China
Shenzhen Bay Lab, Greater Bay Biomed InnoCtr, Shenzhen 518036, Peoples R China
Shenzhen Peking Univ, Hong Kong Univ Sci & Technol, Med Ctr, Biomed Res Inst, Shenzhen 518036, Peoples R China
HKUST Shenzhen Res Inst, Shenzhen 518057, Peoples R China
Keywords CHLOROPHYLL-BINDING PROTEINS
PHASE-SEPARATION
HYDROGELS
TRANSITION
COMPLEXES
Issue Date 9-Jun-2022
Publisher NATURE COMMUNICATIONS
Abstract Membraneless organelles (MLOs) formed via protein phase separation have great implications for both physiological and pathological processes. However, the inability to precisely control the bioactivities of MLOs has hindered our understanding of their roles in biology, not to mention their translational applications. Here, by combining intrinsically disordered domains such as RGG and mussel-foot proteins, we create an in cellulo protein phase separation system, of which various biological activities can be introduced via metal-mediated protein immobilization and further controlled by the water-soluble chlorophyll protein (WSCP)-a remarkably stable, red-light-responsive singlet oxygen generator. The WSCP-laden protein condensates undergo a liquid-to-solid phase transition on light exposure, due to oxidative crosslinking, providing a means to control catalysis within synthetic MLOs. Moreover, these photoresponsive condensates, which retain the light-induced phase-transition behavior in living cells, exhibit marked membrane localization, reminiscent of the semi-membrane-bound compartments like postsynaptic densities in nervous systems. Together, this engineered system provides an approach toward controllable synthetic MLOs and, alongside its light-induced phase transition, may well serve to emulate and explore the aging process at the subcellular or even molecular level. Membraneless organelles play vital cellular roles, and control over their formation and state could have varied applications. Here, the authors develop photoresponsive synthetic condensates whose activity can be controlled through the use of light to trigger liquid-to-solid phase transition.
URI http://hdl.handle.net/20.500.11897/647791
DOI 10.1038/s41467-022-30933-0
Indexed SCI(E)
Appears in Collections: 化学生物学与生物技术学院

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