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Structural basis of SALM5-induced PTPδ dimerization for synaptic differentiation

Author

Listed:
  • Zhaohan Lin

    (Peking University Health Science Center)

  • Jianmei Liu

    (Peking University Health Science Center)

  • Huandi Ding

    (Peking University Health Science Center)

  • Fei Xu

    (Peking University Health Science Center)

  • Heli Liu

    (Peking University Health Science Center)

Abstract

SALM5, a synaptic adhesion molecule implicated in autism, induces presynaptic differentiation through binding to the LAR family receptor protein tyrosine phosphatases (LAR-RPTPs) that have been highlighted as presynaptic hubs for synapse formation. The mechanisms underlying SALM5/LAR-RPTP interaction remain unsolved. Here we report crystal structures of human SALM5 LRR-Ig alone and in complex with human PTPδ Ig1–3 (MeA−). Distinct from other LAR-RPTP ligands, SALM5 mainly exists as a dimer with LRR domains from two protomers packed in an antiparallel fashion. In the 2:2 heterotetrameric SALM5/PTPδ complex, a SALM5 dimer bridges two separate PTPδ molecules. Structure-guided mutations and heterologous synapse formation assays demonstrate that dimerization of SALM5 is prerequisite for its functionality in inducing synaptic differentiation. This study presents a structural template for the SALM family and reveals a mechanism for how a synaptic adhesion molecule directly induces cis-dimerization of LAR-RPTPs into higher-order signaling assembly.

Suggested Citation

  • Zhaohan Lin & Jianmei Liu & Huandi Ding & Fei Xu & Heli Liu, 2018. "Structural basis of SALM5-induced PTPδ dimerization for synaptic differentiation," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02414-2
    DOI: 10.1038/s41467-017-02414-2
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    Cited by:

    1. Christos Gogou & J. Wouter Beugelink & Cátia P. Frias & Leanid Kresik & Natalia Jaroszynska & Uwe Drescher & Bert J. C. Janssen & Robert Hindges & Dimphna H. Meijer, 2024. "Alternative splicing controls teneurin-3 compact dimer formation for neuronal recognition," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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