SHANK3 gene mutations associated with autism facilitate ligand binding to the shank3 ankyrin repeat region

Abstract

Background: Missense mutations in the SHANK3 gene have been detected in autism patients. Results: A mutation in the conserved SPN region of Shank3 improves ligand binding to the ankyrin repeats. Conclusion: The SPN domain regulates accessibility of the ankyrin repeats through an intramolecular interaction. Significance: Autism-associated mutations of Shank3 result in gain-of-function with respect to specific interaction partners. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.