3cve | pdb_00003cve
Crystal Structure of the carboxy terminus of Homer1
Structural highlights
Function[HOME1_RAT] Postsynaptic density scaffolding protein. Binds and cross-links cytoplasmic regions of GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2, SHANK1 and SHANK3. By physically linking GRM1 and GRM5 with ER-associated ITPR1 receptors, it aids the coupling of surface receptors to intracellular calcium release. May also couple GRM1 to PI3 kinase through its interaction with AGAP2. Differentially regulates the functions of the calcium activated channel ryanodine receptors RYR1 and RYR2. Isoform 1 decreases the activity of RYR2, and increases the activity of RYR1, whereas isoform 3 counteracts the effects by competing for binding sites. Isoform 1 regulates the trafficking and surface expression of GRM5. Isoform 3 acts as a natural dominant negative, in dynamic competition with constitutively expressed isoform 1, and isoform 2 to regulate synaptic metabotropic glutamate function. Isoform 3, may be involved in the structural changes that occur at synapses during long-lasting neuronal plasticity and development.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. The postsynaptic density proteins Homer and Shank form a polymeric network structure.,Hayashi MK, Tang C, Verpelli C, Narayanan R, Stearns MH, Xu RM, Li H, Sala C, Hayashi Y Cell. 2009 Apr 3;137(1):159-71. PMID:19345194[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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