9qux
From Proteopedia
Solution structure of the Homer1 EVH1 domain
Structural highlights
FunctionHOME1_MOUSE 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. Isoform 1 regulates the trafficking and surface expression of GRM5. 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 5 counteracts the effects by competing for binding sites. Isoform 3 regulates the trafficking and surface expression of GRM5. Isoform 5 acts as a natural dominant negative, in dynamic competition with constitutively expressed isoform 1, isoform 2 and isoform 3 to regulate synaptic metabotropic glutamate function. Isoform 5, may be involved in the structural changes that occur at synapses during long-lasting neuronal plasticity and development (By similarity). Forms a high-order complex with SHANK1, which in turn is necessary for the structural and functional integrity of dendritic spines (By similarity). Negatively regulates T cell activation by inhibiting the calcineurin-NFAT pathway. Acts by competing with calcineurin/PPP3CA for NFAT protein binding, hence preventing NFAT activation by PPP3CA (By similarity).[UniProtKB:Q86YM7][UniProtKB:Q9Z214] Publication Abstract from PubMedHomer proteins are modular scaffold molecules that constitute an integral part of the protein network within the postsynaptic density. Full-length Homer1 forms a large homotetramer via a long coiled coil region, and can interact with proline-rich target sequences with its globular EVH1 domain. Here we report an atomistic model of the Homer1 coiled coil region along with the NMR solution structure and backbone dynamics of its EVH1 domain, with implications for the organization of the full-length tetramer. Compared to the already available EVH1 structures, our NMR ensemble exhibits subtle differences, mostly in and around its partner binding region, suggesting the presence of ligand-induced conformational transitions. Molecular dynamics simulations of the long coiled coil reveal distinct regions with different stability and flexibility, with the N-terminal part of the coiled coil exhibiting the largest motions. Interestingly, this segment is highly conserved, pointing to the functional relevance of the observed dynamical features. Our results indicate previously unexplored aspects of the flexibility of the full-length Homer1 tetramer that might contribute to the dynamic rearrangements of the postsynaptic protein network linked to its functional transitions. Structural Modeling and Dynamics of the Full-Length Homer1 Multimer.,Kalman ZE, Czajlik A, Maruzs B, Farkas F, Pap I, Homonnay C, Klumpler T, Batta G, Gaspari Z, Peterfia B Proteins. 2025 Nov 21. doi: 10.1002/prot.70091. PMID:41267651[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Large Structures | Mus musculus | Batta G | Czajlik A | Fanni F | Gaspari Z | Maruzs B | Peterfia BF
