Crystallization and low-resolution structure solution of the SALM3-PTPσ synaptic adhesion complex

Synaptic adhesion molecules are major organizers of the neuronal network and play a crucial role in the regulation of synapse development and maintenance in the brain. Synaptic adhesion-like molecules (SALMs) and leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-PTPs) are adhesion protein families with established synaptic function. Dysfunction of several synaptic adhesion molecules has been linked to cognitive disorders such as autism spectrum disorders and schizophrenia. A recent study of the binding and complex structure of SALM3 and PTP sigma using small-angle X-ray scattering revealed a 2:2 complex similar to that observed for the interaction of human SALM5 and PTP sigma. However, the molecular structure of the SALM3-PTP sigma complex remains to be determined beyond the small-angle X-ray scattering model. Here, the expression, purification, crystallization and initial 6.5 angstrom resolution structure of the mouse SALM3-PTP sigma complex are reported, which further verifies the formation of a 2:2 trans-heterotetrameric complex similar to the crystal structure of human SALM5-PTP delta and validates the architecture of the previously reported small-angle scattering-based solution structure of the SALM3-PTP sigma complex. Details of the protein expression and purification, crystal optimization trials, and the initial structure solution and data analysis are provided.

Automated summary

Synaptic adhesion molecules are crucial for neuronal network organization and synapse development. Dysfunction of these molecules is associated with cognitive disorders. A recent study reveals the structure of the mouse SALM3-PTP sigma complex, providing further insight into the role of these proteins in synaptic function.