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Imperfect interface of Beclin1 coiled-coil domain regulates homodimer and heterodimer formation with Atg14L and UVRAG

Author

Listed:
  • Xiaohua Li

    (State Key Laboratory of Chirosciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, PR China.)

  • Liqiang He

    (Mount Sinai School of Medicine, Friedman Brain Institute)

  • Ka Hing Che

    (State Key Laboratory of Chirosciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, PR China.)

  • Sarah F. Funderburk

    (Mount Sinai School of Medicine, Friedman Brain Institute)

  • Lifeng Pan

    (State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, PR China.)

  • Nina Pan

    (Mount Sinai School of Medicine, Friedman Brain Institute)

  • Mingjie Zhang

    (State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, PR China.)

  • Zhenyu Yue

    (Mount Sinai School of Medicine, Friedman Brain Institute)

  • Yanxiang Zhao

    (State Key Laboratory of Chirosciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, PR China.)

Abstract

Beclin 1 is a core component of the Class III Phosphatidylinositol 3-Kinase VPS34 complex. The coiled coil domain of Beclin 1 serves as an interaction platform for assembly of distinct Atg14L- and UVRAG-containing complexes to modulate VPS34 activity. Here we report the crystal structure of the coiled coil domain that forms an antiparallel dimer and is rendered metastable by a series of 'imperfect' a-d' pairings at its coiled coil interface. Atg14L and UVRAG promote the transition of metastable homodimeric Beclin 1 to heterodimeric Beclin1-Atg14L/UVRAG assembly. Beclin 1 mutants with their 'imperfect' a-d' pairings modified to enhance self-interaction, show distinctively altered interactions with Atg14L or UVRAG. These results suggest that specific utilization of the dimer interface and modulation of the homodimer–heterodimer transition by Beclin 1-interacting partners may underlie the molecular mechanism that controls the formation of various Beclin1–VPS34 subcomplexes to exert their effect on an array of VPS34-related activities, including autophagy.

Suggested Citation

  • Xiaohua Li & Liqiang He & Ka Hing Che & Sarah F. Funderburk & Lifeng Pan & Nina Pan & Mingjie Zhang & Zhenyu Yue & Yanxiang Zhao, 2012. "Imperfect interface of Beclin1 coiled-coil domain regulates homodimer and heterodimer formation with Atg14L and UVRAG," Nature Communications, Nature, vol. 3(1), pages 1-11, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1648
    DOI: 10.1038/ncomms1648
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