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Updated: May 30, 2026

Using Scaffold Liposomes to Reconstitute Lipid-proximal Protein-protein Interactions In Vitro
Published on: January 11, 2017
Liprin-mediated large signaling complex organization revealed by the liprin-α/CASK and liprin-α/liprin-β complex
Zhiyi Wei1, Suilan Zheng, Samantha A Spangler
1Division of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Abstract:
Liprins are highly conserved scaffold proteins that regulate cell adhesion, cell migration, and synapse development by binding to diverse target proteins. The molecular basis governing liprin/target interactions is poorly understood. The liprin-α2/CASK complex structure solved here reveals that the three SAM domains of liprin-α form an integrated supramodule that binds to the CASK kinase-like domain. As supported by biochemical and cellular studies, the interaction between liprin-α and CASK is unique to vertebrates, implying that the liprin-α/CASK interaction is likely to regulate higher-order brain functions in mammals. Consistently, we demonstrate that three recently identified X-linked mental retardation mutants of CASK are defective in binding to liprin-α. We also solved the liprin-α/liprin-β SAM domain complex structure, which uncovers the mechanism underlying liprin heterodimerizaion. Finally, formation of the CASK/liprin-α/liprin-β ternary complex suggests that liprins can mediate assembly of target proteins into large protein complexes capable of regulating numerous cellular activities.
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