[PMID]: | 29348579 |
[Au] Autor: | Lin Z; Liu J; Ding H; Xu F; Liu H |
[Ad] Endereço: | State Key Laboratory of Natural and Biomimetic Drugs & Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China. |
[Ti] Título: | Structural basis of SALM5-induced PTPδ dimerization for synaptic differentiation. |
[So] Source: | Nat Commun;9(1):268, 2018 01 18. |
[Is] ISSN: | 2041-1723 |
[Cp] País de publicação: | England |
[La] Idioma: | eng |
[Ab] Resumo: | 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. |
[Mh] Termos MeSH primário: |
Moléculas de Adesão Celular Neuronais/metabolismo Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo
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[Mh] Termos MeSH secundário: |
Baculoviridae Dimerização Células HEK293 Seres Humanos Domínios de Imunoglobulina Estrutura Quaternária de Proteína
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (Cell Adhesion Molecules, Neuronal); 0 (SALM5 protein, human); EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 2) |
[Em] Mês de entrada: | 1802 |
[Cu] Atualização por classe: | 180215 |
[Lr] Data última revisão:
| 180215 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 180120 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1038/s41467-017-02414-2 |
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