TY - JOUR
T1 - Tetrameric hub structure of postsynaptic scaffolding protein Homer
AU - Hayashi, Mariko Kato
AU - Ames, Heather M.
AU - Hayashi, Yasunori
PY - 2006/8/16
Y1 - 2006/8/16
N2 - Homer is a crucial postsynaptic scaffolding protein involved in both maintenance and activity-induced plasticity of the synapse. However, its quaternary structure has yet to be determined. We conducted a series of biophysical experiments that provide the first evidence that Homer forms a tetramer via its coiled-coil domain, in which all subunits are aligned in parallel orientation. To test the importance of the tetrameric structure for functionality, we engineered dimeric and tetrameric Homer by deleting a part of coiled-coil domain or replacing it with artificially engineered dimeric or tetrameric coiled-coil domain from a yeast protein. The structure-activity relationship was determined by assaying cocluster formation with its ligand in heterologous cells, distribution in dendritic spines, and turnover rate of protein exist in dendritic spines. Our results provide the first insight into the structure of native Homer protein as a tetramer and the functional significance conferred by that structure.
AB - Homer is a crucial postsynaptic scaffolding protein involved in both maintenance and activity-induced plasticity of the synapse. However, its quaternary structure has yet to be determined. We conducted a series of biophysical experiments that provide the first evidence that Homer forms a tetramer via its coiled-coil domain, in which all subunits are aligned in parallel orientation. To test the importance of the tetrameric structure for functionality, we engineered dimeric and tetrameric Homer by deleting a part of coiled-coil domain or replacing it with artificially engineered dimeric or tetrameric coiled-coil domain from a yeast protein. The structure-activity relationship was determined by assaying cocluster formation with its ligand in heterologous cells, distribution in dendritic spines, and turnover rate of protein exist in dendritic spines. Our results provide the first insight into the structure of native Homer protein as a tetramer and the functional significance conferred by that structure.
KW - Coiled-coil
KW - Homer
KW - Metabotropic glutamate receptor
KW - Quaternary structure
KW - Scaffolding protein
KW - Synapse
UR - http://www.scopus.com/inward/record.url?scp=33748126215&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748126215&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.2731-06.2006
DO - 10.1523/JNEUROSCI.2731-06.2006
M3 - Article
C2 - 16914674
AN - SCOPUS:33748126215
VL - 26
SP - 8492
EP - 8501
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 33
ER -