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Structural insights into selective interaction between type IIa receptor protein tyrosine phosphatases and Liprin-α
- Source :
- Nature Communications, Vol 11, Iss 1, Pp 1-10 (2020), Nature Communications
- Publication Year :
- 2020
- Publisher :
- Nature Portfolio, 2020.
-
Abstract
- Synapse formation is induced by transsynaptic interaction of neuronal cell-adhesion molecules termed synaptic organizers. Type IIa receptor protein tyrosine phosphatases (IIa RPTPs) function as presynaptic organizers. The cytoplasmic domain of IIa RPTPs consists of two phosphatase domains, and the membrane-distal one (D2) is essential for synapse formation. Liprin-α, which is an active zone protein critical for synapse formation, interacts with D2 via its C-terminal domain composed of three tandem sterile alpha motifs (tSAM). Structural mechanisms of this critical interaction for synapse formation remain elusive. Here, we report the crystal structure of the complex between mouse PTPδ D2 and Liprin-α3 tSAM at 1.91 Å resolution. PTPδ D2 interacts with the N-terminal helix and the first and second SAMs (SAM1 and SAM2, respectively) of Liprin-α3. Structure-based mutational analyses in vitro and in cellulo demonstrate that the interactions with Liprin-α SAM1 and SAM2 are essential for the binding and synaptogenic activity.<br />Synaptic organizers are cell-adhesion molecules capable of inducing synaptic differentiation through transsynaptic interactions. Here the authors present the crystal structure of the intracellular interaction between the synaptic organizer PTPδ and Liprin-α to reveal the structural mechanism of intracellular molecular interactions for IIa-RPTP-mediated synapse formation.
- Subjects :
- Models, Molecular
0301 basic medicine
Science
Vesicular Transport Proteins
General Physics and Astronomy
Molecular neuroscience
Article
General Biochemistry, Genetics and Molecular Biology
Mice
03 medical and health sciences
0302 clinical medicine
Protein Domains
Animals
lcsh:Science
X-ray crystallography
Multidisciplinary
Receptor-Like Protein Tyrosine Phosphatases, Class 2
General Chemistry
Synaptic development
030104 developmental biology
Synapses
lcsh:Q
Crystallization
030217 neurology & neurosurgery
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....0f2559cbb58485f05fa21c5af3712c91