The postsynaptic density proteins Homer and Shank form a polymeric network structure.
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.
Hayashi
Mariko Kato
MK
RIKEN-MIT Neuroscience Research Center, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. hayashim@mit.edu
Tang
Chunyan
C
Verpelli
Chiara
C
Narayanan
Radhakrishnan
R
Stearns
Marissa H
MH
Xu
Rui-Ming
RM
Li
Huilin
H
Sala
Carlo
C
Hayashi
Yasunori
Y
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D000076122:Disks Large Homolog 4 Protein; D000072233:Homer Scaffolding Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D013569:Synapses
D002352:Carrier Proteins; C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D000072233:Homer Scaffolding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C122162:SHANK2 protein, human; C033652:postsynaptic density proteins