5zz9
From Proteopedia
Crystal structure of Homer2 EVH1/Drebrin PPXXF complex
Structural highlights
Function[HOME2_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. Isoforms can be differently regulated and may play an important role in maintaining the plasticity at glutamatergic synapses. [DREB_HUMAN] Drebrins might play some role in cell migration, extension of neuronal processes and plasticity of dendrites. Required for actin polymerization at immunological synapses (IS) and for CXCR4 recruitment to IS.[1] Publication Abstract from PubMedDrebrin is an actin bundling protein that plays critical roles in synaptic spine development and plasticity. Homer, one of the most abundant scaffolding proteins in postsynaptic density, interacts with Drebrin's C-terminal PPXXF motifs using its Ena/VASP homology 1 (EVH1) domain. However, the molecular mechanism and biological function of this interaction remain unclear. Here we show that Homer specifically binds to the first but not the second PPXXF motif in Drebrin. The crystal structure of Drebrin-Homer binding motif 1 in complex with Homer EVH1 reveals a consensus Homer EVH1 binding motif. Homer tetramer promotes actin bundling activity of Drebrin in vitro and stimulates Drebrin-induced filopodia formation and elongation in cells. We further show that monomeric Homer1a antagonizes Homer1b in promoting Drebrin-stimulated actin bundling. Our study suggests a potential regulatory role of Homer1 in modulating excitatory synaptic spine homeostatic scaling via binding to Drebrin. Homer Tetramer Promotes Actin Bundling Activity of Drebrin.,Li Z, Liu H, Li J, Yang Q, Feng Z, Li Y, Yang H, Yu C, Wan J, Liu W, Zhang M Structure. 2018 Nov 5. pii: S0969-2126(18)30372-1. doi:, 10.1016/j.str.2018.10.011. PMID:30503778[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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