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6BD2

Complex of 14-3-3 theta with an IRSp53 peptide doubly-phosphorylated at T340 and S366

6BD2 の概要
エントリーDOI10.2210/pdb6bd2/pdb
分子名称14-3-3 protein theta, Insulin receptor substrate protein of 53 kDa, peptide (IRSp53), DI(HYDROXYETHYL)ETHER, ... (8 entities in total)
機能のキーワードphosphate binding protein, protein complex, cytoskeleton regulation, cell motility, signaling protein
由来する生物種Homo sapiens (Human)
詳細
タンパク質・核酸の鎖数3
化学式量合計60608.83
構造登録者
Kast, D.J.,Dominguez, R. (登録日: 2017-10-20, 公開日: 2018-10-24, 最終更新日: 2024-10-16)
主引用文献Kast, D.J.,Dominguez, R.
Mechanism of IRSp53 inhibition by 14-3-3.
Nat Commun, 10:483-483, 2019
Cited by
PubMed Abstract: 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.
PubMed: 30696821
DOI: 10.1038/s41467-019-08317-8
主引用文献が同じPDBエントリー
実験手法
X-RAY DIFFRACTION (2.9 Å)
構造検証レポート
Validation report summary of 6bd2
検証レポート(詳細版)ダウンロードをダウンロード

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件を2024-12-18に公開中

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