The structure of SALM5 suggests a dimeric assembly for the presynaptic RPTP ligand recognition.

Sudeep Karki, Prodeep Paudel, Celeste Paula Eloise Sele, Alexander V. Shkumatov, Tommi Antero Kajander

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Synaptic adhesion molecules play a crucial role in the regulation of synapse development and maintenance. Recently, several families of leucine-rich repeat (LRR) domain-containing neuronal adhesion molecules have been characterised, including netrin-G ligands, LRRTMs and the synaptic adhesion-like molecule (SALM) family proteins. Most of these are expressed at the excitatory glutamatergic synapses, and dysfunctions of these genes are genetically linked with cognitive disorders, such as autism spectrum disorders and schizophrenia. The SALM family proteins SALM3 and SALM5, similar to SLITRKs, have been shown to bind to the presynaptic receptor protein tyrosine phosphatase (RPTP) family ligands. Here, we present the 3.1 Å crystal structure of the SALM5 LRR-Ig-domain construct and biophysical studies that verify the crystallographic results. We show that SALM1, SALM3 and SALM5 form similar dimeric structures, in which the LRR domains form the dimer interface. Both SALM3 and SALM5 bind to RPTP immunoglobulin domains with micromolar affinity. SALM3 shows a clear preference for the RPTP ligands with the meB splice insert. Our structural studies and sequence conservation analysis suggests a ligand-binding site and mechanism for RPTP binding via the dimeric LRR domain region.
Original languageEnglish
JournalProtein Engineering, Design and Selection
Volume31
Issue number5
Pages (from-to)147-157
Number of pages11
ISSN1741-0126
DOIs
Publication statusPublished - May 2018
MoE publication typeA1 Journal article-refereed

Fields of Science

  • adhesion
  • crystal structure
  • leucine-rich repeat
  • SALM
  • synapse
  • EXCITATORY SYNAPSE DEVELOPMENT
  • PROTEIN-TYROSINE PHOSPHATASES
  • ADHESION-LIKE MOLECULES
  • NERVOUS-SYSTEM
  • PTP-SIGMA
  • LAR-RPTPS
  • FAMILY
  • COMPLEX
  • REPLACEMENT
  • REFINEMENT
  • 1182 Biochemistry, cell and molecular biology

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