Cell
Volume 137, Issue 1, 3 April 2009, Pages 159-171
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Article
The Postsynaptic Density Proteins Homer and Shank Form a Polymeric Network Structure

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Summary

The postsynaptic density (PSD) is crucial for synaptic functions, but the molecular architecture retaining its structure and components remains elusive. Homer and Shank are among the most abundant scaffolding proteins in the PSD, working synergistically for maturation of dendritic spines. Here, we demonstrate that Homer and Shank, together, form a mesh-like matrix structure. Crystallographic analysis of this region revealed a pair of parallel dimeric coiled coils intercalated in a tail-to-tail fashion to form a tetramer, giving rise to the unique configuration of a pair of N-terminal EVH1 domains at each end of the coiled coil. In neurons, the tetramerization is required for structural integrity of the dendritic spines and recruitment of proteins to synapses. We propose that the Homer-Shank complex serves as a structural framework and as an assembly platform for other PSD proteins.

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6

Present address: Graduate Program in Neuroscience, Department of Biology, Brandeis University, Waltham, MA 02453, USA

7

Present address: Institute of Biophysics, Chinese Academy of Sciences, 15 Da Tun Road, Beijing 100101, China