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    Home > Biochemistry News > Biotechnology News > "Nature", a joint team at Westlake University, published a paper: For the first time, the precise head-to-head design of transfilm-hole proteins was achieved.

    "Nature", a joint team at Westlake University, published a paper: For the first time, the precise head-to-head design of transfilm-hole proteins was achieved.

    • Last Update: 2020-09-20
    • Source: Internet
    • Author: User
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    Dr. Chunfu Xu of the University of Washington and Professor David Baker of the School of Life Sciences at Westlake University are co-authors of the paper, as are the co-authors of the paper, professors William A. Catterall and David Baker of the University of Washington.
    , a number of researchers from Osaka University and Cambridge University have also made important contributions to the study.
    Part 1 Understand this study from three basic concepts: membrane protein, channel protein/transfilm protein, and protein design.
    protein refers to the protein on the biofilm, is the main undertaker of biofilm function, mediates the material exchange and information transmission between the cell and the external environment, and is an important participant in energy metabolism.
    if we think of cells as a room, the membrane protein is the window of the room, where sunlight and air are constantly exchanged through the different windows of the room.
    channel protein, is a kind of membrane protein, equivalent to one of the windows of this room, as a channel for the transport of substances across the membrane, it plays a vital role in complex physiological activities such as nerve signal transmission, cellular programmed death, is the drug target of many major human diseases, but also as a protein tool is widely used in biotechnology and research.
    the transfilm protein designed by this study is attached to the channel protein.
    protein design is the core technology in the field of synthetic biology and an emerging frontier discipline.
    protein design by arranging the amino acid sequence of protein, so that it can spontaneously fold to form the required three-dimensional structure, and has certain functions.
    Protein's head-to-head design, which is based entirely on biophysical and biochemical principles, does not rely on existing natural protein structures, and building and designing proteins with new structures and functions from the beginning can help us explore the entire protein sequence folding space.
    than the evolution of proteins in nature, artificially designed proteins, can better meet our specific needs in terms of performance.
    part 2 Lupelong, what did they do? In this study, Lu Peilong Labs, together with a team of researchers, successfully designed two transfilm proteins (Figure 1) consisting of two layers of ɑ helix concentric rings, which can selectively penetrate different molecular sizes and electrolytic solutes.
    , the researchers ɑ a water-soluble form of pore protein consisting of 12 spirals and 16 spirals by parameterizing the structure of the spiral.
    , the aperture of the 12 helix perforated protein (hexerome) is about 3.3 ? The aperture of the 16 helix perforated protein (octomer) is about 10 ?
    By recombining the expression, purification, identification and structural verification of the design hole protein, the researchers demonstrated that the designed pore protein is very stable in nature (e.g., the structure is better resistant to high temperatures than the natural protein) and has a three-dimensional structure consistent with the computational design model.
    , the researchers designed a corresponding transfilm protein.
    electrophysiological experiments have shown that 12 helix transmechanical channel proteins can penetrate ions and have a selective choice of potassium ions;
    In liposome experiments, 16 helix transfilm nanopore proteins can penetrate fluorescent molecules with a molecular weight of about 1000 Daltons, while 12 helix channel proteins cannot;
    , the researchers analyzed the frozen electroscopic structure of 16 helix-span nano-hole proteins, which is very consistent with the design model and proves the accuracy of the design method developed from the beginning.
    This study is the first time in the world to achieve accurate cross-membrane protein head-to-head design, help people better understand the material transfilm transport, that is, cells in the process of metabolism and other life activities of normal material exchange, for the artificial design of transfilm proteins with important functions has laid a solid foundation.
    also opens the door to the possible application of artificial protein follow-up, and is expected to provide new detection methods for nano-porous gene sequencing, molecular detection and other biotechnology.
    For example, the artificial design of nano-hole proteins with special channel structures can be applied to nano-hole sequencing technology to improve the accuracy of DNA nano-hole sequencing technology, and the artificial design of new matching gate-controlled channel proteins will be able to promote channel-based molecular detection technology.
    is the equivalent of us designing different "windows" in a room for different functions.
    Part 3's biggest challenge is to "control its shape" Lu Peilong's long-term commitment to protein design direction, and as early as 2018, he achieved the precise design of multiple three-dimensional structures of transfilm proteins, demonstrating that computer-designed protein sequences can spontaneously fold in a membrane environment to form stable 3D structures consistent with the design model (the results were published in science journal https://science.sciencemag.org/content/359/6379/1042).
    this study is based on the latest breakthroughs in previous research results.
    Its difficulty is that the transfilm protein/ channel protein, like the transfilm protein, belongs to membrane protein, but with a larger than the surface area and relatively low density of molecular in-molecule interaction, from the beginning to design transmeanor protein is more difficult;
    That is, in the course of the study, how to design the sequence of amino acids, spontaneous formation of a specific structure of the pore protein, so that the protein on a small size "grow into a specific appearance", and has a specific transport function, is the study of the difficult point. The
    team worked on two versions of the design, the first version of the pore protein in space has a more curly super-helix, so there is no stable pore protein;
    , the Lu Peilong Research Group at Westlake University will continue to provide humans with new protein design methods and protein tools that do not exist in nature to meet the needs of the biotechnology and biomedical fields through protein design.
    In this study, the design of protein from the beginning was supported by the high-performance computing platform of West Lake University, the frozen electroscope data was collected from the frozen electroscope platform of West Lake University, and the protein mass spectrometography analysis was completed on the mass spectrometum platform of West Lake University.
    .
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