Structural basis of SALM3 dimerization and synaptic adhesion complex formation with PTPσ

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dc.contributor University of Helsinki, Institute of Biotechnology en
dc.contributor University of Helsinki, University Management en
dc.contributor.author Karki, Sudeep
dc.contributor.author Shkumatov, Alexander V.
dc.contributor.author Bae, Sungwon
dc.contributor.author Kim, Hyeonho
dc.contributor.author Ko, Jaewon
dc.contributor.author Kajander, Tommi
dc.date.accessioned 2020-11-02T10:49:01Z
dc.date.available 2020-11-02T10:49:01Z
dc.date.issued 2020-07-14
dc.identifier.citation Karki , S , Shkumatov , A V , Bae , S , Kim , H , Ko , J & Kajander , T 2020 , ' Structural basis of SALM3 dimerization and synaptic adhesion complex formation with PTPσ ' , Scientific Reports , vol. 10 , no. 1 , 11557 . https://doi.org/10.1038/s41598-020-68502-4 en
dc.identifier.issn 2045-2322
dc.identifier.other PURE: 140599989
dc.identifier.other PURE UUID: 3789b834-2b8f-4dcf-90d8-d6f321e8918a
dc.identifier.other WOS: 000550627400015
dc.identifier.other ORCID: /0000-0002-5094-227X/work/83052221
dc.identifier.other ORCID: /0000-0003-3851-1204/work/83054326
dc.identifier.uri http://hdl.handle.net/10138/321014
dc.description.abstract Synaptic adhesion molecules play an important role in the formation, maintenance and refinement of neuronal connectivity. Recently, several leucine rich repeat (LRR) domain containing neuronal adhesion molecules have been characterized including netrin G-ligands, SLITRKs and the synaptic adhesion-like molecules (SALMs). Dysregulation of these adhesion molecules have been genetically and functionally linked to various neurological disorders. Here we investigated the molecular structure and mechanism of ligand interactions for the postsynaptic SALM3 adhesion protein with its presynaptic ligand, receptor protein tyrosine phosphatase sigma (PTP sigma). We solved the crystal structure of the dimerized LRR domain of SALM3, revealing the conserved structural features and mechanism of dimerization. Furthermore, we determined the complex structure of SALM3 with PTP sigma using small angle X-ray scattering, revealing a 2:2 complex similar to that observed for SALM5. Solution studies unraveled additional flexibility for the complex structure, but validated the uniform mode of action for SALM3 and SALM5 to promote synapse formation. The relevance of the key interface residues was further confirmed by mutational analysis with cellular binding assays and artificial synapse formation assays. Collectively, our results suggest that SALM3 dimerization is a pre-requisite for the SALM3-PTP sigma complex to exert synaptogenic activity. en
dc.format.extent 13
dc.language.iso eng
dc.relation.ispartof Scientific Reports
dc.rights en
dc.subject 1182 Biochemistry, cell and molecular biology en
dc.subject LAR-RPTPS en
dc.subject TRANSMEMBRANE PROTEINS en
dc.subject FAMILY en
dc.subject REFINEMENT en
dc.subject MOLECULES en
dc.subject INTERACTS en
dc.subject QUALITY en
dc.title Structural basis of SALM3 dimerization and synaptic adhesion complex formation with PTPσ en
dc.type Article
dc.description.version Peer reviewed
dc.identifier.doi https://doi.org/10.1038/s41598-020-68502-4
dc.type.uri info:eu-repo/semantics/other
dc.type.uri info:eu-repo/semantics/publishedVersion
dc.contributor.pbl
dc.contributor.pbl

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