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Submission Date
Fall 2025
Abstract
We developed a 3D printed model to better understand the structure and function of the molecule, Pikachurin. Pikachurin is an extracellular matrix scaffold protein that bridges photoreceptor and ON-bipolar cell synapses by linking the presynaptic dystroglycan complex to the postsynaptic receptor GPR179, ensuring precise synaptic alignment essential for normal vision. Pikachurin was discovered in 2008 by a Japanese team at the Osaka Bioscience Institute through a microarray analysis of mouse retinas and was named after the Pokémon, Pikachu, because of its “lightning-fast” function in vision transmission. Although its role in dystroglycanopathy associated visual phenotypes is well recognized, there is no published structural model showing how pikachurin engages α-dystroglycan or how this may influence GPCR linked synaptic signaling. The objective of this study was to computationally model a full length Pikachurin based on available Protein Data Bank (PDB) structures with a focus on evaluating the Ca²⁺ -binding domain as a potential site for glycan-mediated interaction with dystroglycan. Structural modeling using Jmol, AlphaFold and literature-based analysis were used to predict domain organization, Ca²⁺-binding motifs, and predicted interaction sites between Pikachurin with the disaccharide-modified dystroglycan. The analysis showed that Pikachurin contains two Fibronectin Type III domains and a Ca²⁺-binding site that enables high-affinity recognition of glycosylated dystroglycan, supporting its role as a synaptic “bridge” protein. These findings suggest that proper glycosylation of dystroglycan is essential for stable Pikachurin binding and synaptic connectivity, and disruptions in this interaction may lead to impaired synaptic transmission and visual function. Our 3D printed model is based on an AlphaFold structure that was produced using the full nucleic acid sequence of Pikachurin, which combines the Fibronectin Type III (FN3 I, FN3 II), and Laminin G-like (LG1, LG2, and LG3) domains. The polysaccharide from PDB ID 7ZCB is 3D printed and bound to the Asn47 binding site as indicated from the literature. A dystroglycan polysaccharide is also printed and attached to the expected calcium binding site between the LG1 and LG2 domains. The residues (within the LG3 domain) that bind with a GPCR (GPR179) in the to the postsynaptic membrane are also highlighted. Through the use of this 3D molecular model, we are better able to understand and explain the story of how Pikachurin is embedded in the extracellular matrix and connected to the presynaptic neuron.
Recommended Citation
Belur, Mohit; Raval, Khushi; Chelagiri, Riya; Mehta, Rani; Schmitt Lavin, Emily; and Sikora, Arthur, "Modeling the Extracellular Matrix-Like Retinal Protein Pikachurin and its Binding to α-Dystroglycan and GPCR (GPR179)" (2025). Protein Modeling Reports. 23.
https://nsuworks.nova.edu/protein_modeling_reports/23