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

Näytä kaikki kuvailutiedot



Pysyväisosoite

http://hdl.handle.net/10138/321014

Lähdeviite

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

Julkaisun nimi: Structural basis of SALM3 dimerization and synaptic adhesion complex formation with PTPσ
Tekijä: Karki, Sudeep; Shkumatov, Alexander V.; Bae, Sungwon; Kim, Hyeonho; Ko, Jaewon; Kajander, Tommi
Muu tekijä: University of Helsinki, Institute of Biotechnology
University of Helsinki, University Management
Päiväys: 2020-07-14
Kieli: eng
Sivumäärä: 13
Kuuluu julkaisusarjaan: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/321014
Tiivistelmä: 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.
Avainsanat: 1182 Biochemistry, cell and molecular biology
LAR-RPTPS
TRANSMEMBRANE PROTEINS
FAMILY
REFINEMENT
MOLECULES
INTERACTS
QUALITY
Tekijänoikeustiedot:


Tiedostot

Latausmäärä yhteensä: Ladataan...

Tiedosto(t) Koko Formaatti Näytä
s41598_020_68502_4.pdf 5.949MB PDF Avaa tiedosto

Viite kuuluu kokoelmiin:

Näytä kaikki kuvailutiedot