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

Area of Science:

• Neuroscience
• Structural Biology
• Molecular Biology

Background:

• Synaptic adhesion molecules organize neuronal networks and regulate synapse development and maintenance.
• Synaptic adhesion-like molecules (SALMs) and leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-PTPs) are key adhesion protein families.
• Dysfunction in these molecules is linked to cognitive disorders like autism spectrum disorders and schizophrenia.

Purpose of the Study:

• To determine the molecular structure of the mouse SALM3-PTPσ complex.
• To verify the formation of a 2:2 trans-heterotetrameric complex.
• To validate previous small-angle X-ray scattering (SAXS) based solution structure models.

Main Methods:

• Protein expression and purification of mouse SALM3 and PTPσ.
• Crystallization trials and optimization.
• X-ray crystallography to determine the initial 6.5 Å resolution structure.

Main Results:

• Successfully expressed and purified the mouse SALM3-PTPσ complex.
• Obtained crystals and determined an initial structure at 6.5 Å resolution.
• Confirmed the formation of a 2:2 trans-heterotetrameric complex, consistent with previous SAXS data and the SALM5-PTPδ complex structure.

Conclusions:

• The crystal structure validates the previously reported SAXS-based solution structure of the SALM3-PTPσ complex.
• The findings reinforce the conserved 2:2 complex architecture across different SALM-PTP interactions.
• This structural information is vital for understanding the role of SALM-PTP interactions in synaptic function and cognitive disorders.