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Understanding CRY2 interactions for optical control of intracellular signaling

Author

Listed:
  • Liting Duan

    (Stanford University)

  • Jen Hope

    (Stanford University)

  • Qunxiang Ong

    (Stanford University)

  • Hsin-Ya Lou

    (Stanford University)

  • Namdoo Kim

    (Stanford University
    Stanford University
    Stanford University)

  • Comfrey McCarthy

    (Northeastern University)

  • Victor Acero

    (Pennsylvania State University)

  • Michael Z. Lin

    (Stanford University
    Stanford University
    Stanford University)

  • Bianxiao Cui

    (Stanford University)

Abstract

Arabidopsis cryptochrome 2 (CRY2) can simultaneously undergo light-dependent CRY2–CRY2 homo-oligomerization and CRY2–CIB1 hetero-dimerization, both of which have been widely used to optically control intracellular processes. Applications using CRY2–CIB1 interaction desire minimal CRY2 homo-oligomerization to avoid unintended complications, while those utilizing CRY2–CRY2 interaction prefer robust homo-oligomerization. However, selecting the type of CRY2 interaction has not been possible as the molecular mechanisms underlying CRY2 interactions are unknown. Here we report CRY2–CIB1 and CRY2–CRY2 interactions are governed by well-separated protein interfaces at the two termini of CRY2. N-terminal charges are critical for CRY2–CIB1 interaction. Moreover, two C-terminal charges impact CRY2 homo-oligomerization, with positive charges facilitating oligomerization and negative charges inhibiting it. By engineering C-terminal charges, we develop CRY2high and CRY2low with elevated or suppressed oligomerization respectively, which we use to tune the levels of Raf/MEK/ERK signaling. These results contribute to our understanding of the mechanisms underlying light-induced CRY2 interactions and enhance the controllability of CRY2-based optogenetic systems.

Suggested Citation

  • Liting Duan & Jen Hope & Qunxiang Ong & Hsin-Ya Lou & Namdoo Kim & Comfrey McCarthy & Victor Acero & Michael Z. Lin & Bianxiao Cui, 2017. "Understanding CRY2 interactions for optical control of intracellular signaling," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00648-8
    DOI: 10.1038/s41467-017-00648-8
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    Cited by:

    1. Dennis Vettkötter & Martin Schneider & Brady D. Goulden & Holger Dill & Jana Liewald & Sandra Zeiler & Julia Guldan & Yilmaz Arda Ateş & Shigeki Watanabe & Alexander Gottschalk, 2022. "Rapid and reversible optogenetic silencing of synaptic transmission by clustering of synaptic vesicles," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Liyuan Zhu & Harold M. McNamara & Jared E. Toettcher, 2023. "Light-switchable transcription factors obtained by direct screening in mammalian cells," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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