6tl8
From Proteopedia
Structural basis of SALM3 dimerization and adhesion complex formation with the presynaptic receptor protein tyrosine phosphatases
Structural highlights
FunctionLRFN4_MOUSE Promotes neurite outgrowth in hippocampal neurons. May play a role in redistributing DLG4 to the cell periphery.[1] [2] CD33_HUMAN Putative adhesion molecule of myelomonocytic-derived cells that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,6-linked sialic acid. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. In the immune response, may act as an inhibitory receptor upon ligand induced tyrosine phosphorylation by recruiting cytoplasmic phosphatase(s) via their SH2 domain(s) that block signal transduction through dephosphorylation of signaling molecules. Induces apoptosis in acute myeloid leukemia (in vitro).[3] [4] Publication Abstract from PubMedSynaptic 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 (PTPsigma). 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 PTPsigma 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-PTPsigma complex to exert synaptogenic activity. Structural basis of SALM3 dimerization and synaptic adhesion complex formation with PTPsigma.,Karki S, Shkumatov AV, Bae S, Kim H, Ko J, Kajander T Sci Rep. 2020 Jul 14;10(1):11557. doi: 10.1038/s41598-020-68502-4. PMID:32665594[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Mus musculus | Bae S | Kajander T | Karki S | Ko J | Shkumatov AV
