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Science 311 (5760): 531-535

Copyright © 2006 by the American Association for the Advancement of Science

An Architectural Framework That May Lie at the Core of the Postsynaptic Density

Marisa K. Baron,1 Tobias M. Boeckers,2 Bianca Vaida,2 Salem Faham,1 Mari Gingery,1 Michael R. Sawaya,1 Danielle Salyer,1 Eckart D. Gundelfinger,3 James U. Bowie1*

Abstract: The postsynaptic density (PSD) is a complex assembly of proteins associated with the postsynaptic membrane that organizes neurotransmitter receptors, signaling pathways, and regulatory elements within a cytoskeletal matrix. Here we show that the sterile alpha motif domain of rat Shank3/ProSAP2, a master scaffolding protein located deep within the PSD, can form large sheets composed of helical fibers stacked side by side. Zn2+, which is found in high concentrations in the PSD, binds tightly to Shank3 and may regulate assembly. Sheets of the Shank protein could form a platform for the construction of the PSD complex.

1 Department of Chemistry and Biochemistry, Molecular Biology Institute and University of California at Los Angeles–U.S. Department of Energy Institute for Genomics and Proteomics, University of California, Los Angeles, 611 Charles E. Young Drive East, Los Angeles, CA 90095-1570, USA.
2 Institute of Anatomy and Cell Biology, University of Ulm, Ulm, Germany.
3 Leibniz Institute for Neurobiology, Post Office Box 1860, D-39008 Magdeburg, Germany.

* To whom correspondence should be addressed. E-mail: bowie{at}mbi.ucla.edu


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