TY - JOUR
T1 - The Postsynaptic Density Proteins Homer and Shank Form a Polymeric Network Structure
AU - Hayashi, Mariko Kato
AU - Tang, Chunyan
AU - Verpelli, Chiara
AU - Narayanan, Radhakrishnan
AU - Stearns, Marissa H.
AU - Xu, Rui Ming
AU - Li, Huilin
AU - Sala, Carlo
AU - Hayashi, Yasunori
N1 - Funding Information:
The crystallographic data were deposited in PDB with accession number 3CVE (Homer1b) and 3CVF (Homer3a). We thank Doctors Amy E. Keating, Robert T. Sauer, Myung Jong Kim, Amanda Mower, Teiichi Furuichi, and Morgan Sheng for helpful discussion and sharing of resources, as well as Ms. Cristina Zucchi and Ms. Valentina Giannini for technical help. The Biophysical Instrumentation Facility for the Study of Complex Macromolecular Systems (supported by NSF-0070319 and NIH GM68762) at Massachusetts Institute of Technology is gratefully acknowledged. This work was supported by RIKEN; NIH grant R01DA17310; Grant-in-Aid from the Ministry of Education, Science, and Culture of Japan (Y.H.); Telethon Italy (grant number GGP06208); Fondazione Cariplo (project number 2006-0779/109251); and Compagnia di San Paolo (project number 2005-1964) (C.S.).
PY - 2009/4/3
Y1 - 2009/4/3
N2 - 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.
AB - 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.
KW - MOLNEURO
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U2 - 10.1016/j.cell.2009.01.050
DO - 10.1016/j.cell.2009.01.050
M3 - Article
C2 - 19345194
AN - SCOPUS:63249131998
SN - 0092-8674
VL - 137
SP - 159
EP - 171
JO - Cell
JF - Cell
IS - 1
ER -