• How mechanical stimuli trigger cellular

    From ScienceDaily@1:317/3 to All on Thu Apr 14 22:30:46 2022
    How mechanical stimuli trigger cellular signalling
    International GPCR research collaboration deciphers structure of active receptors

    Date:
    April 14, 2022
    Source:
    Universita"t Leipzig
    Summary:
    Breathing, seeing, hearing -- the family of G protein-coupled
    receptors (GPCRs) is involved in a variety of physiological
    processes and is also the cause of diverse diseases. Some members
    of the GPCR family respond to mechanical stimuli. Researchers have
    now achieved a milestone on the way to understanding the mechanism
    by which this receptor class is activated.

    They were able to describe the structure of specific active
    receptors.



    FULL STORY ========================================================================== Breathing, seeing, hearing -- the family of G protein-coupled receptors
    (GPCRs) is involved in a variety of physiological processes and is also
    the cause of diverse diseases. As has now been discovered by a team of scientists led by Professor Ines Liebscher from Leipzig University, some members of the GPCR family respond to mechanical stimuli. In collaboration
    with Chinese research groups, they have achieved another milestone on
    the way to understanding the mechanism by which this receptor class is activated. For the first time, they were able to describe the structure
    of specific active receptors. Their findings have now been published in
    the journalNature.


    ========================================================================== "GPCRs are involved in almost all physiological processes in the
    body. GPCRs allow humans to see, control their immune system, direct
    hormone balance," explained Professor Ines Liebscher from the Rudolf Scho"nheimer Institute of Biochemistry at the Faculty of Medicine,
    emphasising: "They have been the focus of our research for many years
    now, and research on GPCRs is of such outstanding importance because
    the majority of approved drugs target this receptor family." GPCRs are receptors that transmit their signals via so-called G proteins, which
    is why they are also called G protein-coupled receptors -- or GPCRs
    for short.

    The researchers in Leipzig focus their work on a special class of
    receptors, known as adhesion GPCRs. In collaboration with several
    Chinese teams of scientists, the research groups led by Professor
    Ines Liebscher and Professor Torsten Scho"neberg have now been able to
    describe the structure of special receptor molecules in their active
    state. This data supports findings from seven years ago at the Leipzig institute that these receptors are activated by a tethered agonist
    within the molecule. Furthermore, the Leipzig researchers showed that mechanical stimuli play a crucial role in the activation by the tethered agonist. It is still not fully understood how our body's own cells are
    able to interpret mechanics -- in the form of vibration, gravitational
    forces, relative cell movement or swelling -- as a signal. "Our research
    has established the basis for our partners from China to structurally
    elucidate a scenario of how mechanical stimuli are recognised in the
    molecule and transmitted as signals," said Liebscher, a medical scientist
    and biochemist.

    "The results can be found in the current study." Functional nature of mechanosensitive receptors elucidated "About one-third of the GPCR family
    are still orphans, meaning that either their function or activation is
    unknown. With our current research, we have made a decisive contribution
    to better understanding GPCR structures," said co- author Scho"neberg,
    director of the Rudolf Scho"nheimer Institute of Biochemistry. "The new
    study findings are of landmark importance when it comes to developing
    future forms of therapy," concluded Liebscher. She is a member of the
    steering committee in the EU-funded COST Action Adher'n Rise CA18240,
    which she successfully secured in 2019. This network of scientists from
    28 European countries aims to promote, stimulate and implement research on adhesion G protein-coupled receptors (aGPCRs) "from bench to bedside." The latest findings and approaches to adhesion GPCR research will also be
    presented at the international conference 4GPCRnet, of which Professor Liebscher is co- organiser. This high-level meeting will be held on 26
    to 29 September 2022 on Leipzig University's Augustusplatz campus.

    The current research project is part of Collaborative Research Centre 1423 "Structural Dynamics of GPCR Activation and Signaling," a research network funded by the German Research Foundation, led by Leipzig University
    and also involving the Martin Luther University Halle-Wittenberg,
    Charite' - - Universita"tsmedizin Berlin and the Max Delbru"ck Center
    for Molecular Medicine. Researchers with backgrounds in biochemistry, biomedicine and computational science collaborate across the boundaries
    of their respective institutions and disciplines for a comprehensive understanding of the structure and dynamics of GPCRs.


    ========================================================================== Story Source: Materials provided by Universita"t_Leipzig. Original
    written by Peggy Darius.

    Note: Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Yu-Qi Ping, Peng Xiao, Fan Yang, Ru-Jia Zhao, Sheng-Chao Guo,
    Xu Yan,
    Xiang Wu, Chao Zhang, Yan Lu, Fenghui Zhao, Fulai Zhou, Yue-Tong Xi,
    Wanchao Yin, Feng-Zhen Liu, Dong-Fang He, Dao-Lai Zhang, Zhong-Liang
    Zhu, Yi Jiang, Lutao Du, Shi-Qing Feng, Torsten Scho"neberg,
    Ines Liebscher, H. Eric Xu, Jin-Peng Sun. Structural basis for the
    tethered peptide activation of adhesion GPCRs. Nature, 2022; DOI:
    10.1038/s41586-022- 04619-y ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/04/220414110756.htm

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