6bcy

Complex of 14-3-3 theta with an IRSp53 peptide phosphorylated at T360

spinqualitylabelsall models 6bcy, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6bcy is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: 1PE, MG, PE4, PEG, PG4, TPO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BAIP2_HUMAN Adapter protein that links membrane-bound small G-proteins to cytoplasmic effector proteins. Necessary for CDC42-mediated reorganization of the actin cytoskeleton and for RAC1-mediated membrane ruffling. Involved in the regulation of the actin cytoskeleton by WASF family members and the Arp2/3 complex. Plays a role in neurite growth. Acts syngeristically with ENAH to promote filipodia formation. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection. Publication Abstract from PubMed Filopodia are precursors of dendritic spines and polarized cell migration. The I-BAR-domain protein IRSp53 is a key regulator of filopodia dynamics that couples Rho-GTPase signaling to cytoskeleton and membrane remodeling, playing essential roles in neuronal development and cell motility. Here, we describe the structural-functional basis for 14-3-3-dependent inhibition of IRSp53. Phosphoproteomics, quantitative binding and crystallographic studies demonstrate that 14-3-3 binds to two pairs of phosphorylation sites in IRSp53. Using bicistronic expression, we obtain an IRSp53 heterodimer in which only one subunit is phosphorylated, and show that each subunit of IRSp53 independently binds one 14-3-3 dimer. A FRET-sensor assay using natively phosphorylated IRSp53 reveals opposite conformational changes upon binding of activatory (Cdc42, Eps8) or inhibitory (14-3-3) inputs. Finally, we show that 14-3-3 inhibits IRSp53 binding to membranes. Collectively, our findings support a mechanism whereby phosphorylation-dependent inhibition of IRSp53 by 14-3-3 counters membrane binding and interactions with Cdc42 and downstream cytoskeletal effectors. Mechanism of IRSp53 inhibition by 14-3-3.,Kast DJ, Dominguez R Nat Commun. 2019 Jan 29;10(1):483. doi: 10.1038/s41467-019-08317-8. PMID:30696821 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 14-3-3 protein 3D structures

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