2018
DOI: 10.1038/s41467-017-02414-2
|View full text |Cite
|
Sign up to set email alerts
|

Structural basis of SALM5-induced PTPδ dimerization for synaptic differentiation

Abstract: SALM5, a synaptic adhesion molecule implicated in autism, induces presynaptic differentiation through binding to the LAR family receptor protein tyrosine phosphatases (LARRPTPs) 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 fr… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

10
74
0

Year Published

2018
2018
2022
2022

Publication Types

Select...
4
1
1

Relationship

2
4

Authors

Journals

citations
Cited by 42 publications
(84 citation statements)
references
References 68 publications
10
74
0
Order By: Relevance
“…S1). Thus, we conclude that the dimerization mechanism through the LRR domains is conserved in the family, generating a unique dimeric post-synaptic 17,19 (see below), and SALM4 regulates the function of SALM3 by cis-inhibition, most likely through heterodimer formation 16 . Function of SALM2 remains unclear, but it appears to be able to bind the LAR-RPTP receptors 18 , whereas the function of SALM1 appears quite different, with reported involvement in actin mediated post-synaptic neurexin clustering, and no synapse formation activity reported 28 , and has much lower affinity (with K d ca.…”
Section: Dimerization Through the Lrr Domain Is A Defining Feature Ofmentioning
confidence: 78%
See 4 more Smart Citations
“…S1). Thus, we conclude that the dimerization mechanism through the LRR domains is conserved in the family, generating a unique dimeric post-synaptic 17,19 (see below), and SALM4 regulates the function of SALM3 by cis-inhibition, most likely through heterodimer formation 16 . Function of SALM2 remains unclear, but it appears to be able to bind the LAR-RPTP receptors 18 , whereas the function of SALM1 appears quite different, with reported involvement in actin mediated post-synaptic neurexin clustering, and no synapse formation activity reported 28 , and has much lower affinity (with K d ca.…”
Section: Dimerization Through the Lrr Domain Is A Defining Feature Ofmentioning
confidence: 78%
“…The binding interface in SALM3-PTPσ complex is formed by three interaction sites ( Fig. 4b, Supplementary Table S2), similar to SALM5-PTPδ (PDB 5XNP, 5XWT) 17,18 17 . Here, we generated mutations in SALM3 on these three sites (Fig 4b, c) in order to validate the SALM3 complex structure.…”
Section: Mutational Analysis Of Salm3-ptpσ Interfacementioning
confidence: 97%
See 3 more Smart Citations