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Solution structures of the SH 3 domains from Shank scaffold proteins and their interactions with Cav1.3 calcium channels
Author(s) -
Ishida Hiroaki,
Skorobogatov Anton,
Yamniuk Aaron P.,
Vogel Hans J.
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13209
Subject(s) - scaffold protein , postsynaptic density , chemistry , cav1.2 , protein–protein interaction , plasma protein binding , binding site , biophysics , postsynaptic potential , microbiology and biotechnology , calcium channel , calcium , biochemistry , biology , signal transduction , receptor , organic chemistry
Shank proteins are abundant scaffold proteins in the postsynaptic density ( PSD ) region of brain synapses. Mutations in Shank proteins are associated with autism, schizophrenia, and Alzheimer's disease. To gain insights into Shank protein interactions at the PSD , we determined the solution structures of the src homology 3 ( SH 3) domains of all three mammalian Shank proteins. Our findings indicate that they have identical and typical SH 3 folding motifs, but unusual target‐binding pockets. An investigation into the interaction between the Shank SH 3 domains and the proline‐rich region of the Cav1.3 calcium channel revealed an atypical interaction in which the highly acidic specificity binding pocket of the SH 3 domains binds to a Cav1.3 region containing a cluster of three Arg residues. Our study provides insights into Shank SH 3‐mediated interactions.