Probing the Key Interactions between Human Atg5 and Atg16 Proteins: A Prospective Application of Molecular Modeling

Authors

  • Zhixiong Zhao,

    1. State Key Laboratory of Bioorganic & Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032 (P.R. China)
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    • These authors contributed equally to this work.

  • Zhengxi Zhang,

    1. State Key Laboratory of Bioorganic & Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032 (P.R. China)
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    • These authors contributed equally to this work.

  • Dr. Yan Li,

    1. State Key Laboratory of Bioorganic & Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032 (P.R. China)
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  • Mi Zhou,

    1. State Key Laboratory of Bioorganic & Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032 (P.R. China)
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  • Dr. Xun Li,

    1. State Key Laboratory of Bioorganic & Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032 (P.R. China)
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  • Prof. Biao Yu,

    1. State Key Laboratory of Bioorganic & Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032 (P.R. China)
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  • Prof. Renxiao Wang

    Corresponding author
    1. State Key Laboratory of Bioorganic & Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032 (P.R. China)
    • State Key Laboratory of Bioorganic & Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032 (P.R. China)
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Abstract

original image

Breaking things down: Disruption of the Atg5–Atg16 protein–protein interaction is a potential strategy for the development of effective inhibitors of autophagy. Using a structural model of the human Atg5–Atg16 complex, a total of 30 Atg16-based peptides were designed and tested for their binding affinity to Atg5. A number of these peptides exhibited binding affinities in the low micromolar range. Furthermore, three Atg16 residues were identified as the key factors in Atg5 binding.

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